Comparison of Allogeneic Stem Cell Transplantation and Best Supportive Care in Elderly Patients with Advanced MDS.
Authors: Kröger Nicolaus , Putter Hein , Brand Ronald , Kündgen Andrea , de Witte T. M. , Germing Ulrich 
Published: October 2019

Abstract 3363

Poster Board III-251

The introduction of reduced-intensity conditioning regimens and the reduction of therapy-related complications have increased the upper age limit of the recipient and encouraging results of allogeneic stem cell transplantation in MDS-patients have been reported up to the age of 70 years. However, whether elderly patients with MDS should undergo allogeneic stem cell transplantation is a matter of debate. We used a multi-state approach to compare the outcome in elderly advanced MDS patients (aged 55 – 69 years) with RAEB or RAEB-t who received only best supportive care and were reported to the Düsseldorf registry (n = 137), to those who received allogeneic stem cell transplantation and were reported to the European Group for Blood and Marrow Transplantation (EBMT) (n = 246). A simple direct comparison is biased by non-observable patients who die before transplant. We used left-truncation and modelling of transition probabilities to obtain estimates of survival after diagnosis; moreover scenario analyses were performed to quantify sensitivity for untestable assumptions and to estimate survival for various strategies depending on the time between diagnosis and transplant.

In the non-transplant cohort, diagnosis was RAEB in 100 (73%) and RAEB-t in 37 patients (27%). The median age of the 83 male and 54 female patients was 62 years. Cytogenetic data were available in 79 patients and reported to be abnormal in 60 %. In the transplant cohort 168 were male and 78 female. Disease status at diagnosis was RAEB (70%) and RAEB-t (30%). At time of transplantation, diagnosis was RAEB (54%), RAEB-t (34%) and transformed secondary acute leukemia (12%). Transplantation from HLA-identical sibling (n = 175) or unrelated donor (n = 71) was performed after standard myeloablative (n = 76) or reduced-intensity conditioning (n = 170). Cytogenetic data were available in 88 patients and reported to be abnormal in 60 %.

The median follow-up of the non-transplant cohort was 21 and of the transplant cohort measured from date of transplant was 64 months. Median time between date of diagnosis and date of transplant was 7 months. The cumulative incidence of non-relapse mortality of the transplant cohort at 1 year and 3 years was 15% and 31%, respectively. The cumulative incidence of relapse was 14% and 29% at the same time points. Univariately, after accounting for left truncation and modelling of the death rate before transplant, the hazard ratio for survival is estimated as 0.72 in favour of transplant (95 % CI: 0.53 – 0.99; p = 0.04). After adjustment for year of diagnosis, the hazard ratio remained unchanged (the year of diagnosis was neither a confounder nor it showed interaction). In a multivariate analysis, adjusting for age at diagnosis, sub-diagnosis (RAEB vs. RAEB-t), cytogenetics (abnormal vs. normal), the hazard ratio for transplantation versus no-transplantation: 0.77 (95 % CI: 0.44 – 0.99; p = 0.1) while the other hazard ratio's were: 1.4 for “age > 60” (95 % CI: 1.10 – 1.70; p = 0.02); 1.20 for “RAEB-t” (95 % CI: 0.92 – 1.48; p = 0.2) and 1.46 for “abnormal cytogenetics” (95 % CI: 1.16 – 1.76; p = 0.01).

Despite of an estimated benefit of allogeneic SCT in comparison to best supportive care in elderly MDS patients with RAEB or RAEB-t, this conclusion evidently relies on several statistical assumptions, notably about the selection mechanism among patients scheduled for transplant but never reaching that treatment. Only a prospective trial comparing hypomethylating agents with a reduced-intensity transplant approach according to donor availability is capable of answering this question appropriately but our analysis may provide sufficient indication that such a randomization is both needed and ethically justified.

Disclosures:

No relevant conflicts of interest to declare.