No Survival Benefit From HSCT in Patients with Ph+ ALL in First Complete Molecular Remission

A retrospective study demonstrated that patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with induction therapy, including tyrosine kinase inhibitors (TKIs), and who had attained complete molecular remission (CMR) within 90 days of diagnosis had no survival benefit from allogeneic hematopoietic stem cell transplantation (HSCT) in first remission.

The study, led by Armin Ghobadi, MD, the Clinical Director of the Center for Gene and Cellular Immunotherapy at the Washington University School of Medicine in St. Louis, also demonstrated that transplant was associated with a lower incidence of disease relapse but did increase the mortality related to treatment.

The study was based on data from 230 patients and took place at five transplant centers in the US: Washington University School of Medicine, MD Anderson Cancer Center, City of Hope Cancer Center, H. Lee Moffitt Cancer Center, and Memorial Sloan Kettering Cancer Center. Participants were retrospectively identified and included if they met the following criteria:

• Aged 18 years and older
• Diagnosed with Ph+ ALL from May 2001 to December 2018 and achieved a complete remission (CR) with CMR within 90 days of diagnosis by quantitative polymerase chain reaction and remained undetectable on subsequent evaluations up to 90 days after diagnosis

Patients were excluded if they were previously diagnosed with chronic myeloid leukemia, had died less than 90 days after diagnosis, or had less than 90 days of follow-up.

Patients were split into two cohorts: allogeneic HSCT (n=98) and non-HSCT (n=132). Although the allogeneic HSCT cohort was younger and had a better performance status, multivariable analysis showed that transplant did not improve overall survival ([OS] adjusted hazard ratio [aHR], 1.05; 95% Cl, 0.63-1.73) or relapse-free survival ([RFS] aHR, 0.86; 95% CI,0.54-1.37) compared to the non-HSCT cohort.

Furthermore, although allogeneic HSCT was associated with a lower cumulative incidence of relapse (aHR, 0.32; 95% CI, 0.17-0.62), it also increased non-relapse mortality (aHR, 2.59; 95% CI, 1.37-4.89).

“Our analysis demonstrates that, compared with non-[HSCT] approaches with modern induction regimens and TKIs, [allogeneic HSCT] in [first] CR for patients achieving CMR within 90 days of diagnosis is not associated with an improvement in OS or RFS,” the authors wrote.

Ghobadi A, Slade M, Kantarjian HM, et al. The role of allogeneic transplant for adult PH+ ALL in CR1 with complete molecular remission: a retrospective analysis. Blood. 2022. doi:10.1182/blood.2022016194