Contributions
Abstract: EP948
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Myelodysplastic syndromes (MDS) have been described as a complication of chemotherapy with alkylating agents in patients treated for multiple myeloma (MM). However, there are also reports on the extremely rare coincidence of MDS and MM in the absence of preceding chemotherapy or together at the time of diagnosis. The exact causes of the uncommon co-occurrence of de novo MM and MDS are not known and therefore further studies are needed. Recurrent chromosomal aberrations are well characterized in both diagnoses and cytogenomic examination is part of the prognostic stratification of patients with MM and MDS as well. In MM, the most common findings are translocations involving the IgH gene (14q32), monosomy 13/del(13q), gain of 1q21, and deletion of the TP53 gene (17p13). In MDS, these are mainly del(5q), monosomy 7/del(7q), trisomy 8 and del(20q). It can be assumed that cases of two distinct clones underlying MDS and MM may often be underdiagnosed.
Aims
The aim of the study was to perform a retrospective analysis of cytogenomic findings in a sufficiently large group of patients with MM, to identify cases with the independent cell clones bearing MM and MDS specific chromosomal aberrations and to assess its frequency and effects on patient survival.
Methods
In the 2004-2020 we examined the karyotype of 1415 patients with MM using a combination of cytogenomic methods. Conventional cytogenetic analysis was performed on bone marrow cells cultivated for 24 hours without stimulation. The presence of the most common MM aberrations in immunofluorescently labeled plasma cells was studied using the cIg-FISH method with locus specific DNA probes for detection of: IgH translocations, deletion of TP53 gene, deletion 13q/monosomy 13 and loss/gain of 1p32/1q21 (Abbott Vysis, Kreatech, MetaSystems). The clonality of aberrations characteristic for MDS was confirmed using I-FISH on the whole bone marrow. Complex karyotypes were analyzed with the mFISH/mBAND method (MetaSystems).
Results
We detected a total of 13 patients with the simultaneous occurrence of independent clones with MM and MDS aberrations (5 males, 8 females with median age 66 years). Using the cIg-FISH method, we proved MM aberrations in 11 of them, in 2 remaining patients no aberrations were detected by specific panel. In nine cases, a myeloid cell clone was detected at repeated cytogenetic examination after the MM therapy [1x del(20q), 2x del(5q), 1x trisomy 8, 1x del(11q), 4x complex karyotype]. The median time to occurrence of myeloid clone was 40.5 months (range 3.5 to 169 months). The malignant MM clone persisted with the onset of secondary MDS in 5/9 cases. In addition, we identified four previously untreated MM patients with clonal aberrations characteristic of MDS at the first cytogenetic examination [2x del(20q), 1x del(7q), 1x del(5q) and trisomy 8]. Eight of 13 patients died 0.3 to 19 months from the occurrence of MDS cell clone (median 7 months).
Conclusion
We report nine cases of secondary MDS after MM therapy and four untreated patients with rare coincidence of MM and primary MDS. In this study, the finding of MDS specific aberrations was associated with a worsened prognosis. Therefore, especially in longer-treated patients with MM, it is necessary to take into account the risk of the onset of secondary myeloid disease and to focus on these aberrations in cytogenomic analysis.
Supported by RVO-VFN64165 and ProgresQ28/LF1.
Keyword(s): Chromosomal abnormality, Multiple myeloma, Myelodysplasia, Secondary
Abstract: EP948
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Myelodysplastic syndromes (MDS) have been described as a complication of chemotherapy with alkylating agents in patients treated for multiple myeloma (MM). However, there are also reports on the extremely rare coincidence of MDS and MM in the absence of preceding chemotherapy or together at the time of diagnosis. The exact causes of the uncommon co-occurrence of de novo MM and MDS are not known and therefore further studies are needed. Recurrent chromosomal aberrations are well characterized in both diagnoses and cytogenomic examination is part of the prognostic stratification of patients with MM and MDS as well. In MM, the most common findings are translocations involving the IgH gene (14q32), monosomy 13/del(13q), gain of 1q21, and deletion of the TP53 gene (17p13). In MDS, these are mainly del(5q), monosomy 7/del(7q), trisomy 8 and del(20q). It can be assumed that cases of two distinct clones underlying MDS and MM may often be underdiagnosed.
Aims
The aim of the study was to perform a retrospective analysis of cytogenomic findings in a sufficiently large group of patients with MM, to identify cases with the independent cell clones bearing MM and MDS specific chromosomal aberrations and to assess its frequency and effects on patient survival.
Methods
In the 2004-2020 we examined the karyotype of 1415 patients with MM using a combination of cytogenomic methods. Conventional cytogenetic analysis was performed on bone marrow cells cultivated for 24 hours without stimulation. The presence of the most common MM aberrations in immunofluorescently labeled plasma cells was studied using the cIg-FISH method with locus specific DNA probes for detection of: IgH translocations, deletion of TP53 gene, deletion 13q/monosomy 13 and loss/gain of 1p32/1q21 (Abbott Vysis, Kreatech, MetaSystems). The clonality of aberrations characteristic for MDS was confirmed using I-FISH on the whole bone marrow. Complex karyotypes were analyzed with the mFISH/mBAND method (MetaSystems).
Results
We detected a total of 13 patients with the simultaneous occurrence of independent clones with MM and MDS aberrations (5 males, 8 females with median age 66 years). Using the cIg-FISH method, we proved MM aberrations in 11 of them, in 2 remaining patients no aberrations were detected by specific panel. In nine cases, a myeloid cell clone was detected at repeated cytogenetic examination after the MM therapy [1x del(20q), 2x del(5q), 1x trisomy 8, 1x del(11q), 4x complex karyotype]. The median time to occurrence of myeloid clone was 40.5 months (range 3.5 to 169 months). The malignant MM clone persisted with the onset of secondary MDS in 5/9 cases. In addition, we identified four previously untreated MM patients with clonal aberrations characteristic of MDS at the first cytogenetic examination [2x del(20q), 1x del(7q), 1x del(5q) and trisomy 8]. Eight of 13 patients died 0.3 to 19 months from the occurrence of MDS cell clone (median 7 months).
Conclusion
We report nine cases of secondary MDS after MM therapy and four untreated patients with rare coincidence of MM and primary MDS. In this study, the finding of MDS specific aberrations was associated with a worsened prognosis. Therefore, especially in longer-treated patients with MM, it is necessary to take into account the risk of the onset of secondary myeloid disease and to focus on these aberrations in cytogenomic analysis.
Supported by RVO-VFN64165 and ProgresQ28/LF1.
Keyword(s): Chromosomal abnormality, Multiple myeloma, Myelodysplasia, Secondary