Discussion:
In this report, we described a case of NS that developed during
follow-up for AA with monosomy 7 without HSCT. We performed a literature
review of cases with both diseases, and analyzed genetic factors that
may predispose to their onset.
Previous studies have reported that clonal evolution is a major
complication for AA treated with IST2), 3). Patel et
al. reported that in a large cohort of 666 adult subjects with severe AA
treated with IST, monosomy 7 appeared in 38 subjects, and 33 of the 38
subjects developed it within 5 years of starting
IST4).
NS has been described as a clinical form of chronic GVHD, but only a
limited number of cases have been reported1). Kim et
al. reported that a 13-year-old Asian boy developed NS 22 months after
allogeneic HSCT for severe AA possibly due to the effects of chronic
GVHD5). Our case developed NS during IST alone without
HSCT for AA, and to the best of our knowledge, there has been only one
report of a case with a similar course in the past. Abrams et al.
reported a case of 9-year-old boy who presented NS that was
pathologically diagnosed as minimal change NS, and that gradually
progressed to concurrent idiopathic AA6). Prior to the
diagnosis of AA, he had frequent relapses of NS. However, after the
start of IST for AA, the NS remained in remission. Unfortunately, no
information about monosomy 7 was presented in this report.
Recently, several groups have reported germlineSAMD9/9Lmut in addition to somaticGATA2mut as a predisposing factor for
cytopenia, bone marrow failure, and myelodysplastic syndrome with
non-random monosomy 7 or deletion of 7q7). Sahoo et
al. reported that almost half of the myelodysplastic syndrome patients
with monosomy 7 or del(7q) carried mutations in eitherSAMD9/9Lmut (21%) orGATA2mut mutations (30%)8).
They reported that the prevalence of GATA2mutincreased with age, whereas SAMD9/9Lmut were
found at similar frequencies across all age groups. Recently, there was
a case report of a girl with myelodysplasia, infection, growth
restriction, adrenal hypoplasia, genital phenotypes, and enteropathy
(MIRAGE) syndrome caused by a gain-of-function mutation in theSAMD9 gene on chromosome 7 who developed steroid-resistant
NS9).
Based on this background, we examined the case for such genetic
abnormalities, but there were no somatic/germline gene mutations inSAMD9/9Lmut orGATA2mut in our case. The genetic factors
associated with hematopoietic failure and NS are currently unknown, but
it is possible that some common genetic factors exist, because the
patient developed NS when the proportion of cells with monosomy 7 was
increased. The prognosis of the patient appears favorable at this point,
but it will be necessary to carefully monitor the rate of IST tapering,
in the future, including consideration of hematopoiesis and the
proportion of cells with monosomy7.
In conclusion, this is the first detailed report of NS associated with
AA that was treated without HSCT. Some common immunological and genetic
factors might be involved in the development of both AA and NS.
Identification of these factors is expected in the future with the
accumulation of data from more cases of AA and NS.