DISCUSSION
We described three SDS patients who developed solid tumors. Table 1
summarizes their cases and four others previously
published.6-9 All the cancers in our series occurred
during the fifth decade (median: 47 years), whereas the published cases
of cancers in SDS patients appeared slightly earlier (median: 34.5
years; range: 17–43 years). Five (71.4%) of the seven patients were
women, two with breast adenocarcinoma and two with ovarian tumors. All
reported cases had localized or locally advanced disease at diagnosis.
The overall cancer rate for SDS patients in our Registry was 1.9%
(3/155); cancer development was clearly age-related, because all
occurred between 40 and 60 years of age. That rate is not as high as
that for malignant hemopathies,2 but the SDS–cancer
relationship remains a worrying observation. Age was the sole risk
factor identified. None of these cancers was preceded by exposure to
chemotherapy, radiotherapy, immunosuppressive agents or G-CSF therapy.
Notably, among the 21 SDS HSCT patients in our 155-patient cohort, 14
survived >5 years without any diagnosed solid tumor. That
observation contrasts with another model of inherited bone-marrow
failure like Fanconi anemia. The latter is characterized by the
occurrence of solid ENT cancers (head & neck squamous cell carcinoma)
after chemotherapy, in particular post-HSCT.11
The care of the cancer is another concern in SDS patients as their
overall survival lasted <1 year, and death was attributed to
cancer progression or therapeutic complications. Patient #5726 and
patient #5254 received lower first-line treatment doses because of
preexisting neutropenia or thrombocytopenia. These observations
emphasize the difficulty to manage solid cancers in patients with SDS
despite the adaptation of cancer therapeutic guidelines.
Lastly, tissue NGS study in the 2 patients which can be studied
demonstrated the presence of a TP53 pathogenic variant.
Pertinently, the SBDS mutation contains an escape mechanism
consisting of TP53 activation that maintains protein synthesis.
Those gain-of-function variants may generate malignant clones emerging
leading to malignant hemopathies.12 The pathogenicTP53 variants found in #5254 and #5726 raise the possibility of
a hypothetical common mechanism both in SDS hematological clonal
evolution as well as in tissue malignancies13, 14.
Further molecular and cellular studies are needed to understand this
complication in the natural history of SDS in order to treat
it15.
Conflict of Interest: none
Acknowledgements: The French registry is supported by grants from Inserm
and by a grant from the 111 les arts. This project is supported by
constant and unlimited support of the Association Sportive de Saint
Quentin Fallavier since 2004 with the unlimited commitment of Mr Gonnot.
The authors thank the association IRIS for her support.