Gamuchirai Tadzimirwa* and Estelle Verburgh* comment on the publication entitled “Long-term outcomes after haploidentical stem cell transplantation for hematologic malignancies” published in Blood Advances.
* Dr Gamuchirai Tadzimirwa, Consultant & Clinical Haematologist at the University of Cape Town Groote Schuur Academic Hospital, Cape Town, South Africa
* Prof Estelle Verburgh, Consultant & BMT Director of the University of Cape Town Groote Schuur Academic Hospital, Cape Town, South Africa
Long-term outcomes after haploidentical stem cell transplantation for hematologic malignancies
Saengboon S, Ciurea S, Popat U, et al. Blood Adv. 2024;8(12):3237-3245. doi:10.1182/bloodadvances.2023010625
Haplo-identical stem cell transplantation (haplo-SCT) has significantly expanded the donor pool for patients with high-risk malignancies. The introduction of post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has markedly improved outcomes, including reductions in GVHD, graft failure, and non-relapse mortality (NRM). Consequently, there is a growing population of haplo-SCT recipients, though long-term data remain limited.
In this paper, Saengboon et al. report on the long-term outcomes of PTCy-based haplo-SCT at MD Anderson Cancer Center. The study retrospectively analyzed the 385 patients who underwent haplo-SCT for high-risk hematologic malignancies, including AML, MDS, ALL, MPN, and lymphoid malignancies, between 2009 and 2019. Note that the median age at transplantation was 48 years. Most patients had AML/MDS (58.2%), underwent reduced-intensity conditioning (88.66%), and received bone marrow transplants (84%). All patients received PTCy-based GVHD prophylaxis.
The study categorized patients into two groups: long-term survivors (disease-free and alive 2 years post-transplant) and short-term survivors (those who relapsed/progressed or died within 2 years post-transplant). The primary endpoints included progression-free survival (PFS) and overall survival (OS) for long-term survivors, while secondary endpoints included cumulative incidence of relapse (CIR), NRM, and GVHD-free relapse-free survival (GRFS).
Of the 385 patients, 183 were short-term survivors, whereas 142 patients were long-term survivors. Although baseline characteristics were similar between the two groups, short-term survivors had a significantly higher proportion of high/very high-risk disease (53% vs. 27%; P < .0001); they were also older (median age 52 vs. 45 years; P = .086), and had a higher hematopoietic cell transplantation-specific comorbidity index >3 (39% vs. 30%; P = .128).
The median follow-up was 50 months, with 4-year PFS and OS rates of 42% and 47%, respectively, for all patients. Among long-term survivors, with a median follow-up of 52 months, the 4-year PFS and OS rates were 94% and 96%, respectively. Notably, age ≥55 years was associated with inferior outcomes in this group, with 4-year and 8-year PFS rates of 85% and 66%, compared to 97% and 88% for those <55 years (P = .0136). Similarly, 4-year and 8-year OS rates were 92% and 70% for patients ≥55 years, versus 97% and 90% for younger patients (P = .0268).
Relapses occurred in 27% of the entire cohort, with a median time to relapse of 6 months and a 4-year CIR of 28%. However, among long-term survivors, only 3% progressed, with a median time to relapse of 46 months and a 4-year CIR of 2.9%.
The estimated 4-year NRM for all patients was 30%, primarily due to infections and GVHD. In the long-term survivor group, only one patient died from relapse, with an estimated 4-year NRM of 3.3%. The most common cause of death in this group was second primary malignancies, particularly non-small cell lung cancer, associated with heavy smoking.
The long-term survivor group exhibited significantly lower rates of grade 3-4 acute GVHD compared to short-term survivors, though the rates of extensive chronic GVHD were not statistically different. The 1-year and 2-year GRFS rates in long-term survivors were 90% and 85%, respectively, compared to 29% and 8% in the short-term disease-free survivor group (P < .0001).
This single center study reports excellent PFS, OS, GRFS, and NRM among long-term survivors of haplo-SCT who remain disease-free 2 years post-transplant. Although observational, these findings provide valuable insights into long-term survival following the high-risk early post-transplant period, and emphasizes the importance of long term clinical surveillance post-SCT. The use of haplo-donors is particularly relevant in population groups and in regions with impaired access to other related, or unrelated, SCT-donors.