Long-term follow-up of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation

Abstract

The outcome of patients with therapy-related myelodysplasia (t-MDS) or t-AML is very poor. The only curative treatment option implements allogeneic hematopoietic cell transplantation (aHCT); however, long-term follow-up data beyond 5 years are scarce. Here we report on a cohort of 79 consecutive patients with a median age of 58 years (range (r): 20-76) at transplantation and a median follow-up of 7.5 years (r: 0.07-19.0). Only 19 (24.1%) patients were in CR before aHCT. Non-relapse mortality and relapse rates were 23% (95% confidence interval, 15-35%) and 42% (32-55%) at 5 years, and 32% (22-46%) and 44% (34-57%) at 10 years, respectively. Disease-free survival (DFS) and overall survival (OS) rates were 35% (24-46%) and 38% (27-49%) at 5 years, and 24% (14-36%) and 24% (13-36%) at 10 years, respectively. Although cytogenetic aberrations were associated with shorter DFS and higher relapse risk, persistent disease at the time of transplantation, an unrelated donor and patient age were not associated with shorter OS. In conclusion, long-term survival beyond 10 years of t-MDS/t-AML patients after aHCT is possible, even for refractory patients. Therefore, early donor search and rapid transplantation are warranted, also to decrease the risk of disease-related deterioration of patients' performance status.Bone Marrow Transplantation (2016) 51, 771-777; doi:10.1038/bmt.2015.338; published online 11 January 2016 INTRODUCTION Cytotoxic agents, especially alkylating and topoisomerase II targeting drugs, as well as ionizing radiotherapy in the successful treatment of most cancer types and to some extent also in nonmalignant diseases, bear a significant long-term risk of developing therapy-related malignancies such as myelodysplasia (t-MDS) and t-AML. 1,2 Despite intensive efforts to reduce the risk of developing t-MDS/t-AML by using fewer cycles of dose-intense chemotherapy for a given primary disease and thus to decrease cumulative doses, this late occurring side effect remains a challenging clinical problem. 3 Treatment of t-MDS/t-AML, which often occurs with other comorbidities, is complex and the outcome of patients treated with low-or even high-dose chemotherapy alone remains poor. Beyond other factors, this is especially attributed to older age, therapy resistance and cytogenetic abnormalities including monosomies or complex karyotypes. 4,5 In recent years, it has become evident that the most successful curative treatment concept for t-MDS/t-AML patients resulting in substantial remission rates implements allogeneic hematopoietic cell transplantation (aHCT). Using a myeloablative conditioning regimen in 77% of patients in a cohort of 868 patients with a median age of 40 years, Litzow et al. 6 reported an overall survival (OS) rate of 22% (95% confidence interval (CI), 19-26%) after 5 years, although the non-relapse mortality (NRM) and relapse rate at that time were 48% (95% CI, 44-51%) and 31% (95% CI, 28-34%), respectively. In another study from the European Group for Blood and Marrow Transplantation, Kröger et al. 7...

Therapy-related myelodysplastic syndromes, or are they?

“…These better outcomes could be secondary to less toxic conditioning regimens leading to better non-relapse mortality. Also, in this study, neither age nor donor type was associated with worse outcomes [104]. Retrospective data from Fianchi et al showed that patients with t-MN who received HCT have better OS than those who did not (58.8 months for allogeneic SCT vs. 12.1 months, P b0.0001) [75].…”

“…Age greater than 35, poor cytogenetics, disease not in remission at time of HCT, and non-sibling related donor or mismatched unrelated donor were associated with poor outcomes. Data from a more recent but smaller cohort suggests improvement in five year OS, 38% [104]. These better outcomes could be secondary to less toxic conditioning regimens leading to better non-relapse mortality.…”

Long-term survival of patients with therapy-related myeloid neoplasms after allogeneic hematopoietic cell transplantation—more than just a myth

“…The authors did not provide mutational data on these patients primarily because it was not being collected routinely in the 1990s and early 2000s. In conclusion, the study by Finke et al 6 show that HCT is feasible and can be used successfully in a fraction of t-MDS/AML patients, and that improved outcomes will require efforts to base transplant decisions on newly available information, some of which will require validation in larger studies or through prospective trials.…”

“…But based on recent data, the clinical course of t-MN in this primary cancer groups would be closer to de novo disease, thus these cases may do well with non-transplant approaches. The study by Finke et al 6 does not elaborate on the characteristics of the long-term survivors with respect to the site and treatment of primary cancers.…”

“…They report on the long-term outcomes of 79 t-AML/MDS patients who underwent allogeneic HCT between 1995 and 2014 that were followed for a median of 7.5 years (0.07-19 years). 6 The cohort in this study was high risk based on several features: a median age of 58 years (35% over the age of 65 years), unfavorable cytogenetics (53%), HCT-comorbidity index (CI) score of 43 (77.2%) and induction failure with initial chemotherapy or progressive disease (42%).…”