Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning: a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation

Abstract

BackgroundMyeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach.MethodsWe analyzed long-term outcomes in a cohort of 1423 AML patients, age ≥50 years, after SCT from HLA-matched siblings, during the years 1997–2005, median follow-up 8.3 years (0.1–17).ResultsThe 10-year leukemia-free survival (LFS) was 31 % (95CI, 27–35) and 32 % (28–35) after MAC and RIC, respectively (P = 0.57). The 10-year GVHD/ relapse-free survival (GRFS), a surrogate for quality of life was 22 % (18–25) and 21 % (18–24), respectively (P = 0.79). The 10-year non-relapse mortality (NRM) was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65–76) and 73 % (67–78) after MAC and RIC, respectively (P = 0.76). Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC.ConclusionsLong-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0347-1) contains supplementary material, which is available to authorized users.

ASBMT Practice Guidelines Committee Survey on Long-Term Follow-Up Clinics for Hematopoietic Cell Transplant Survivors

“…Hematopoietic cell transplantation (HCT) has proven to be a curative treatment for many malignant and nonmalignant conditions, with a growing population of patients now surviving many years post-transplant [1,2]. As therapies for complications such as acute graft-versus-host-disease (GVHD), organ toxicities, and infectious issues have improved, we now face new challenges in managing these long-term survivors [3].…”

Allogeneic haematopoietic stem cell transplantation can improve the prognosis of high-risk paediatric t(8;21) acute myeloid leukaemia in first remission based on MRD-guided treatment.

“…Translocation (8;21) (q22;q22) or RUNX1-RUNX1T1 rearrangement comprises 10%-15% of paediatric acute myeloid leukaemia (AML) and is known to have a favourable outcome [1]. However, approximately 30% of patients ultimately relapse and even with allogeneic haematopoietic stem cell transplantation (allo-HSCT), the prognosis of patients who relapse remains poor [2]. Therefore, the present study aimed to establish a means to identify high-risk patients and determine stratified treatment to reduce disease recurrence and improve survival.…”

Frailty: the missing piece of the pre- hematopoietic cell transplantation assessment?

“…11 Better risk stratification is essential as OS in elderly HSCT recipients remains modest despite improvements with RIC regimen. 2,6,7,12 Although there has been a decline in NRM due to drug toxicities, infections and chronic GVHD (cGVHD) with RIC regimen as well as improved post-HSCT supportive care, long-term NRM in the elderly remains upwards of 20%. 2,6,7,12 As poor risk cytogenetics that portend increased rate of relapse tend to occur more frequently in older patients with hematologic malignancies, long-term relapse rate in the elderly following allogeneic HSCT with RIC remains upwards of 30% and diseasefree survival remains low.…”

“…2,6,7,12 Although there has been a decline in NRM due to drug toxicities, infections and chronic GVHD (cGVHD) with RIC regimen as well as improved post-HSCT supportive care, long-term NRM in the elderly remains upwards of 20%. 2,6,7,12 As poor risk cytogenetics that portend increased rate of relapse tend to occur more frequently in older patients with hematologic malignancies, long-term relapse rate in the elderly following allogeneic HSCT with RIC remains upwards of 30% and diseasefree survival remains low. 2,6,7,13,14 HSCT survivors of all ages are at risk for developing frailty, which has been defined as 'a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death.'…”

“…2,6,7,12 As poor risk cytogenetics that portend increased rate of relapse tend to occur more frequently in older patients with hematologic malignancies, long-term relapse rate in the elderly following allogeneic HSCT with RIC remains upwards of 30% and diseasefree survival remains low. 2,6,7,13,14 HSCT survivors of all ages are at risk for developing frailty, which has been defined as 'a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death.' 15 Exposure to high intensity chemotherapy and cGVHD in HSCT recipients are risk factors for frailty.…”