Patients with newly diagnosed transformed Fanconi anemia (FA) have poor outcomes and should achieve complete remission (CR) prior to allogeneic hematopoietic stem cell transplantation (alloHSCT), according to results from a study published in the American Journal of Hematology.

Stefano Giardino, MD, of the hematopoietic stem cell transplantation unit at the Istituto Giannina Gaslini in Italy, and colleagues retrospectively analyzed outcomes of 74 patients with transformed FA (36 male; median age, 14 years); 35 patients had myelodysplastic syndrome, 35 had acute leukemia, and 4 patients had high-risk cytogenetic abnormality. All patients underwent alloHSCT from 1999 to 2016.

The primary end points were overall survival (OS) and event-free survival (EFS). Secondary endpoints included the incidence of grade 2 to 4 acute graft-vs-host disease (AGVHD) and chronic graft-vs-host disease (CGVHD), non-relapse mortality (NRM), and incidence of relapse. To identify potential factors that may influence outcomes, the researchers assessed the type of diagnosis, preHSCT cytoreductive therapies and related toxicities, disease status prior to HSCT, donor type, and conditioning regimen.

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At a median follow-up of 7 years, 5-year OS and EFS were 42% and 39%, respectively; 5-year cumulative incidence relapse and NRM rates were 21% and 40%, respectively. Patients in CR during transplant had better OS than those who still had active disease (OS, 71% vs 37%, respectively; P =.04). No other factors had a significant effect on patient outcomes.

Of 22 patients who received cytoreductive therapy prior to HSCT, 40.9% experienced a grade 3 to grade 4 toxicity event; this did not appear to effect survival after HSCT (3 year OS, toxicity preHSCT 48% vs no toxicity 51%; P  =.98). At 100 days, the cumulative incidence of grade 2 to 4 AGVHD was 38%, and the cumulative incidence of 5-year CGVHD was 40%.

At 5 years, NRM was 40%, while incidence of relapse was 21%. Transplant-related events were the cause of mortality in 81% of patients (34 of 42 deaths).

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Limitations of the study included the retrospective design and incomplete data for some variables. The authors highlighted the large number of patients for this rare disorder as the primary strength.

“In order to optimize the chances of the only curative option for FA in malignant transformation, a sequential cytoreductive therapy followed by HSCT appears a reasonable approach in FA patients with AL, if a previously identified donor is rapidly available,” wrote the authors. “However, since the risk of treatment-related complications is high, these patients should be managed in highly specialized centers and transplant approaches aimed at reducing the occurrence of [GVHD] and transplant-related complications should be prioritized.”


Giardino S, Latour RP, Aljurf M, et al. Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: a retrospective analysis on behalf of EBMT group [published online April 8, 2020]. Am J Hematol. doi: 10.1002/ajh.25810