Long-Term Outcome of Therapy-Related Myelodysplastic Syndromes and Acute Myeloid Leukemias Arising in Patients Treated for Lymphoma or Solid Tumors.
Authors: Milani Raffaella , Palmieri Salvatore , Zanni Manuela , Pollio Filiberto , Dodero Anna , Spina Francesco , Testi Adele , Tarella Corrado , Bernardi Massimo , Gallamini Andrea , Bandini Giuseppe , Benedetti Fabio , Ferrara Felicetto , Corradini Paolo 
Published: April 2020

Abstract
Several studies have shown that therapy-related MDS (tMDS) and AML (tAML) have a poor outcome with very few long-term survivors. Curative treatment strategies are not yet standardized and the role of hematopoietic stem cell transplantation (SCT) is still not fully elucidated in standard care treatment. We performed a retrospective outcome research with the aim of looking at the survival curves of tMDS and tAML patients treated at 7 different Institutions. According to the presence of comorbidities or a matched donor, 71 patients (pts) received the best treatment option based on attending physician opinion: 24 pts (group A) with tAML (n=13, FAB M0, M1, M2, M4) and tMDS (n=7 RAEB-2. n=4 RAEB-1) received allogeneic transplantation, 28 pts (group B) with tAML (n=20, FAB M0, M1, M2, M4, M5) and tMDS (n=3 RAEB-2, n=4 RAEB-1, n=1 RA) received chemotherapy and 19 pts (group C) received supportive care only (n=1 tAML, n=18 low-risk MDS or RAEB-1 (n=5)). Median age was 55 years (range 23–67) in group A, 61 years (range 27–73) in group B and 55 years (range 22–70) in group C. Conventional karyotype analysis was available in 12 pts of group A (n=7 complex, n=1 normal, n=2 isolated del(7q) or monosomy 7, n=1 isolated del(5q), n=1 trisomy 21) and in 15 pts of group B (n=3 complex, n=8 normal, n=1 isolated del(Y), n=1 isolated del(11), n=1 isolated trisomy 11, n=1 isolated trisomy 8). In the group A, all pts, because of age and/or comorbidities, received a fludarabine-based reduced-intensity conditioning followed by allogeneic peripheral blood SCT. Disease status at transplant was categorized as low risk (n=9 CR1 or CR2), high risk (n=3 PR, n=6 PD, n=2 refractory) and 4 pts were treated up-front. The median time from diagnosis to allografting was 6 months (range: 1–80 months). Pts received allogeneic stem cells from HLA-matched siblings (n=16), or HLA-matched unrelated donors (n=6), or haploidentical related donors (n=2). All pts engrafted. Acute GVHD grade II–IV occurred in 6 pts (n=1 post-DLIs), chronic GVHD developed in 6 pts (n=1 post-DLIs). OS at 5 years was 5.5%, the 4-year EFS was 0%, TRM at 100 days and at 1 year were 28%. No statistical differences were observed in TRM, EFS, and OS according to disease status at transplant and diagnosis of tMDS or tAML. DFS for pts in CR at transplant was 23% at 1 year. In the group B, pts received chemotherapy and 11 of them an autologous stem cell transplantation. OS at 5 years was 16%, EFS at 5 years was 10%, DFS at 1 year was 31%. TRM at 5 years was 30%. In the group C, OS was 28% at 5 years. Our data show that, in daily clinical practice, the outcome of patients receiving chemotherapy followed by allogeneic SCT is not improved compared to the patients not having a suitable donor. At the present time, considering the very low chance of cure, in therapy-related disorders the main goal for clinicians should be prevention.