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.