Abstract

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) can be late complications following mutagenic treatment. Limited data is available on the outcome of patients developing therapy-related MDS and AML after treatment for multiple myeloma (MM). We identified 250 patients with therapy-associated MDS or AML in the Duesseldorf MDS registry. Of those, 50 patients were previously diagnosed with multiple myeloma (mm-MDS/AML). We compared them to patients with de novo MDS (n = 4862) and to patients with MDS following other underlying diseases (tMDS) (n = 200). mm-MDS patients and tMDS patients showed similar karyotypes and degrees of cytopenia. However, mm-MDS patients had significantly higher blast counts and more often belonged to the high-risk group according to the International Prognostic Scoring System (IPSS) (both p < 0.05). Although the rate of progression to AML was similar in mm-MDS and tMDS, both transformed significantly more often than de novo MDS (p < 0.05). Median overall survival of patients with mm-MDS (13 months; range: 1–99) and tMDS (13 months; range 0–160) was also similar yet significantly shorter than patients with de novo MDS (32 months; range 0–345 months; p < 0.05). Furthermore, survival of mm-MDS patients was not affected by myeloma activity. Despite significantly more high-risk disease and higher blast cell counts, myeloma-associated MDS-patients show features akin to other tMDS. Survival is similar to other tMDS and irrespective of myeloma remission status or transformation to AML. Thus, patient outcome is not determined by competing clones but rather by MDS governing the stem cell niche.

Highlights

  • Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) can represent late complications following cytotoxic treatment and are summarized as the distinct category “therapy-related myeloid neoplasms” in the current World Health Organization (WHO) classification [1]

  • Our analysis shows that the majority of mm-MDS patients present with high-risk MDS or AML, as reflected by blast count (12% showing more than 20% blasts), karyotype (38% poor risk), International Prognostic Scoring System (IPSS), or rapid disease progression (24 and 39% transformation of MDS to AML, respectively)

  • This is comparable to data from large series of patients with tMDS or tAML, which showed an abnormal karyotype in 75% and 92% of all cases, while an abnormal karyotype was observed in only 51% and 52% of patients with de novo AML/MDS, respectively [20, 21]

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Summary

Introduction

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) can represent late complications following cytotoxic treatment and are summarized as the distinct category “therapy-related myeloid neoplasms” in the current World Health Organization (WHO) classification [1]. They account for approximately 10–20% of all cases of MDS. Progression to AML is usually rapid and often accompanied by relative resistance to conventional chemotherapy [9]. In this retrospective study, we analyzed clinical characteristics, cytogenetic data, risk of AML transformation, and probability of survival of 50 patients with MDS/AML following multiple myeloma therapy (mm-MDS). We compared them with therapy-associated MDS/AML due to other underlying diseases (tAML/tMDS) and with de novo

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