3 Discussion
We report a patient with KMT2A -rearranged ALL who developed
secondary graft failure after CBT with TBI-based MAC and then
experienced autologous hematopoietic recovery with molecular CR of
primary disease. He also had complex chromosomal abnormalities in
recovered autologous hematopoietic cells.
Graft failure can be classified into two groups: primary graft failure,
where the patient never achieves ANC >0.5 ×
109 /L for 3 successive days, and secondary graft
failure, where the patient loses donor cells after initial
engraftment10. This case was considered to have
experienced secondary graft failure, based on the above definitions. A
retrospective study from Olsson et al.11 showed that
54 of 967 patients (5.6%) experienced graft failure after HSCT.
Moreover, in a report of 309 children undergoing allogenic BM
transplantation12, 11 cases (3.6%) of graft failure
occurred, suggesting that graft failure is relatively uncommon.
Non-malignant diseases, reduced-intensity conditioning, lower stem cell
dose, viral infection, and HLA-mismatched grafts are associated with
increased risk of graft failure11,12,13. TBI-based
conditioning is considered to have sufficient immunosuppressive effects
and excellent antitumor effects on malignant hematologic diseases, and
can also enhance the likelihood of neutrophil engraftment in CBT,
regardless of conditioning intensity14. In our case,
secondary graft failure occurred despite the use of TBI-based MAC for
malignant disorder. HLA-mismatched CBT or hemophagocytosis observed in
the BM may have been factors influencing secondary graft failure.
There have been some case reports of autologous recovery following
TBI-based MAC in adult patients with chronic myeloid leukemia
(CML)4,5,6 or (acute myeloid leukemia)
AML7. Moreover, 10 of 291 (3.4%) adult patients with
CML were found to undergo autologous recovery after HSCT followed by
cyclophosphamide + TBI regimen6. In a recent report
from JSHCT8, only 30 of 59,603 children (0.05%)
receiving HSCT, who were registered to JSHCT between 1974 and 2016,
experienced autologous recovery after TBI-based MAC (≥8 Gy). Hence,
autologous hematopoietic recovery after HSCT is rarely reported in
pediatric patients compared with adult patients.
The persistent detection of chromosomal abnormalities in the present
patient raised concerns about the development of myelodysplastic
syndrome (MDS) and leukemia; however, in our case, the pattern of
chromosomal abnormalities was complex, changed randomly, and did not
include MDS/leukemia-related cytogenetic abnormalities such as monosomy
7 and trisomy 8. Further, only 2 of 35 children reported by JSHCT with
persistent detection of chromosomal abnormalities developed MDS/AML,
whereas 19 of them relapsed8. Absence of alloreactive
response was suggested to be the reason for limited therapeutic effects.
In conclusion, we describe a rare pediatric case who underwent secondary
engraftment failure with autologous hematopoietic recovery after CBT
with TBI-based MAC. Given the limited data on autologous recovery in
pediatric patients, long-term follow-up with caution, to monitor for
primary disease relapse or progression to MDS or leukemia, is required.