Abstract

Cytotoxic chemoradiotherapy may lead to the development of tMDS and tAML. These disorders are associated with a poor prognosis with non-transplant therapy. We report outcomes of alloSCT for tMDS and tAML in 868 subjects transplanted between 1990 and 2004 at 211 centers in 33 countries. Subjects were excluded (n=322) if they had a prior disease predisposing to MDS or AML, if they had a diagnosis of tALL or had received a twin or cord blood transplant. 21% were ≤19 years old (yo); 55% were female and 63% had tAML (including 30% with prior tMDS). Prior diagnoses included Hodgkin lymphoma (23%) and non-Hodgkin lymphoma (21%), breast cancer (16%), ALL (12%), sarcoma (8%), germ cell tumor (6%), and autoimmune disorders (5%). There were rare cases (≤3%) of CLL, plasma cell disorders, neuroblastoma, Wilms and CNS tumors or other cancers. Prior treatment was chemotherapy in 43%, chemotherapy and radiation therapy in 51% and radiation therapy alone in 4%. Cytogenetic data (cd) at the time of transplant were known in 84%: good prognosis 4%, intermediate 61% and poor 34%. The IPSS score at diagnosis for subjects with tMDS was intermediate-2 or high in 54%. At transplant, 51% of subjects with tAML were in first complete remission (CR1), 7% ≥CR2, 15% in relapse and 27% were primary induction failures. For the tMDS pts, 37% had been treated with other modalities before receiving an alloSCT. Pre-transplant conditioning regimen was myeloablative (M) 77% and reduced intensity (RI or non-M) in the remainder. Donors were related 38% and unrelated 62%; 66% of the grafts were bone marrow and 34% peripheral blood stem cells. Cumulative incidence of acute GVHD (grade II-IV) @100 days was 39% (95% confidence interval [CI]), 35–42). Outcomes, with a median follow-up of 61 (range, 3–187) months were:

Outcome:5 year probability (95% CI)
Chronic GVHD 30 (27–33) 
Treatment-related mortality (TRM) 48 (44–51) 
Relapse 31 (28–34) 
Disease-free survival (DFS) 21 (18–24) 
Overall survival (OS) 22 (19–26) 
Outcome:5 year probability (95% CI)
Chronic GVHD 30 (27–33) 
Treatment-related mortality (TRM) 48 (44–51) 
Relapse 31 (28–34) 
Disease-free survival (DFS) 21 (18–24) 
Overall survival (OS) 22 (19–26) 

In multivariate analysis (MVA), TRM was significantly higher in subjects >35 yo, in those with a poor (<90%) performance score (PS), with untreated MDS or if a mismatched related or unrelated donor was used. Relapse risk was higher for subjects >35 yo, with preceding ALL or poor prognosis cytogenetics or tAML not in CR. DFS and OS were lower in subjects >35 yo, with poor prognosis cd, AML not in CR or untreated MDS, or with a mismatched related or unrelated donor. Of 649 pts who died, the cause of death was tMDS or tAML in 33% and TRM in the others. The use of a RI or non-M conditioning regimen did not improve outcomes in the MVA. Approximately 20% of pts with tMDS and tAML achieve long term survival following alloSCT. Survival was significantly better in pts <35 yo, with good or intermediate risk cd, disease control at the time of transplant and having a matched related or complete or partially matched-unrelated donor. The 5 year survival was 50% (95% CI, 39–61) with all 4 good risk factors (grf); 25% (95% CI, 20–31) with any 3 grf, 19% (95% CI, 14–24) with any 2 grf, 12% (95%CI, 8–18) with only 1 grf, and only 4% (95%CI, 0–15) without any of these factors. In conclusion, these data may be helpful in guiding clinical decision-making on the role of alloSCT in the management of t-AML and t-MDS.

Author notes

Disclosure: No relevant conflicts of interest to declare.