Autologous Hematopoietic Stem Cell Transplant Shows Safety for Late Treatment Intensification for Ph-Negative ALL

Autologous hematopoietic stem cell transplantation (AHSCT) demonstrated relative efficacy and safety among patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-negative ALL), and showed potential as a treatment particularly effective for those with T-cell precursor (TCP) disease, according to study results published in BMC Cancer.

While previous research has found AHSCT to be associated with improved cancer outcomes in patients with Philadelphia positive ALL (Ph+ ALL), there is limited data on the efficacy of AHSCT for patients with Ph- ALL, including those with BCP- or TCP-ALL. Researchers conducted a retrospective analysis to determine transplant outcomes among patients with Ph- ALL.

The primary end points were leukemia-free survival (LFS), overall survival (OS), relapse incidence (RI), and non-relapse mortality (NRM). Patients (N = 700) who received AHSCT between 1999 and 2020 in first complete remission (CR1) were included. Among the cohort, 64.7% had TCP-ALL and 35.3% had B-cell precursor ALL (BCP-ALL). Minimal residual disease (MRD) status was available for 190 patients, with 87.9% achieving MRD negativity prior to transplant. Patients with BCP-ALL had a higher median age than patients with TCP-ALL (40.9 years vs 31.9 years) and more patients with BCP-ALL were female (42.9% vs 25.4%) compared to the TCP-ALL group.

At 5 years, the LFS (51.7% vs 37.5%; P = .002) and OS (58.3% vs 45.1%; P = .001) were higher among patients with TCP-ALL compared to patients with BCP-ALL. However, RI was lower for patients with TCP-ALL (41.1%) compared to the BCP-ALL group (56.1%; P= .001).

Multivariate analysis results demonstrated patients with  TCP-ALL when compared to patients with BCP-ALL had a lower risk of relapse, (hazard ratio [HR], 0.7; 95% confidence interval [CI], 0.54 to 0.9; P = .006) as well as improved LFS (HR, 0.76; 95% CI, 0.58 to 0.96; P = .023) and OS (HR, 0.75; 95% CI, 0.58 to 0.96; P= .024).

Older age per 10 years among patients with both TCP-ALL and BCP-ALL was associated with higher NRM (HR, 1.49; 95% CI, 1.23 to 1.79; P < .001), as well as lower LFS (HR, 1.1; 95% CI, 1.02 to 1.19; P = .01) and OS (HR, 1.17; 95% CI, 1.08 to 1.28, P < .001). 

Longer time from diagnosis per month of ALL to AHSCT was associated with lower relapse risk (HR, 0.95; 95% CI, 0.91 to 0.99; P= .018), improved LFS (HR, 0.95; 95% CI, 0.9 to 0.99; P = .01), and better OS (HR, 0.94; 95% CI, 0.9 to 0.99, P = .0013).

“Autologous hematopoietic stem cell transplantation is [a] relatively safe option of late treatment intensification in adults with Ph- ALL. The target population should rather be restricted to patients defined as standard risk, particularly, those with negative MRD status,” the researchers concluded.

“AHSCT may be a valuable option especially in patients with TCP-ALL, however it should be proved in prospective clinical trials," they added.

Source:

Swoboda R, Labopin M, Giebel S, et al. Autologous stem cell transplantation for adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission. A study by the Acute Leukemia Working Party of the EBMT. BMC Cancer. Published online April 28, 2025. doi:10.1186/s12885-025-14126-8