Doctors often face the need to make the decision to proceed with allogeneic transplantation in people with MLFS in the face of incomplete data and limited guidance in the literature.9,10,11. A patient with aplastic marrow may not always have certain cytogenetic or molecular characteristics available and, therefore, clinical insight weighs more in treatment decisions. Thus, despite the heterogeneity of our group, we describe its results to help guide doctors in the treatment of this unique population.
Recent literature has supported the concept that CR may not be necessary for allogeneic HCT4,12,13. Unfortunately, the heterogeneity in the classification of disease status in transplantation between NCCN, CIBMTR and the standard criteria of the 2003 IWG made it challenging to evaluate specific outcomes in the MLFS population, thus frustrating the development of evidence-based treatment guidelines. Our data support our hypothesis that MLFS following the formal definition of Cheson et al is sufficient for the success of allogeneic hematopoietic stem cell transplantation, resulting in long-term remission in a substantial part of the patients12,13,14,15. Our results remarkably highlight that the MLFS segment considered aplastic with ANC <200 are particularly high risk and have poor results after transplantation. As such, care should be taken when considering switching to an allogeneic transplant while it is still fully aplastic, without showing any decrease in leukocyte recovery.
According to the reports by Vu et al., Our study found that NRM is high in the MLFS population (35% in our cohort)4. This may be partly the result of our patient population having an average high HCT-CI of 4. An additional finding was 71% (5/7) of those with a surviving cord donor, which is consistent with Milano et al who reported superior results in patients with positive MRD15 and deserves more attention in future prospective studies. Due to the aplastic marrow of several of our patients with MLFS, MRD status has not been obtained, however, this would be an important addition for future studies to help provide a stronger clinical impact and comparison between our findings and previous studies as well.
Our work is additionally limited by a possible selection bias due to the retrospective nature of the study and the heterogeneity in the treatment methods that cannot be avoided when obtaining data retrospectively. This includes variation in clinical judgment that may have impacted the decision to transition patients to allogeneic HCT, as well as the choice of conditioning regime or donor source. In order to reduce bias in relation to the reported data, we guarantee a standardized approach for our review of medical records with sensitivity analysis between evaluators for quality assurance.
As far as we know, our review provides the largest cohort of patients in MLFS assessed after allogeneic HCT, although this is still a limited sample. Our ability to compare populations and draw definitive conclusions is hampered by not having complete NGS or molecular data for all individuals, as well as by the heterogeneity of the donor and the induction of transplantation. Currently, studies available in non-CR patients have proposed that failure to achieve haematological recovery can be a strong indicator of residual disease and suggests poor results; however, our data directly challenge this theory. In addition, our observed low relapse rates and encouraging OS are promising. Our data question, however, whether any extent of hematological recovery should be observed before transplantation, as evidenced when comparing the results between those who were aplastic (ANC <200) or not before HCT. The continuous evaluation of this population is guaranteed. In addition, the collection of future data looking at the results of the transplantation from the other NCCN response criteria described in Table 1 (ie PIF or CRi) can help to put our findings in a broader perspective, as doctors make decisions about when this modality is due.