Allogeneic Related Donor Hematopoietic Cell Transplantation in AML CR1: Beware of Past Invasive Fungal Infections
Authors: Arat Mutlu , Ozcelik Tulay , Guvenc Serkan , Hindilerden Fehmi , Goksoy Hasan Sami , Küçükkaya Reyhan 
Published: October 2019

Abstract
Allogeneic hematopoetic cell transplantation (allo-HCT) is currently the only curative treatment option for non-M3 AML in first or second remission (CR1, CR2). Cytogenetic risk factors, pretransplant disease status and factors apart from leukemia could affect the success of allo-SCT. It is still uncertain that allo-SCT in CR1 has superior efficacy especially for those patients who have cytogenetically standard risk. The optimization of supportive care in last 2 decades decreased early transplant related mortality substantially. In this intent-to treat, single center, retrospective study we analyzed 40 consecutive AML patients who underwent allo-SCT between January 2011 and November 2013 at our centre to determine the role of allo-SCT in CR1 or beyond. Patients were evaluated for overall survival (OS), disease free survival (DFS), early (30 - 100 day) and late (101-365 day) transplant related mortality (TRM). Survival was estimated using the Kaplan–Meier method, and the log-rank test was used to compare survival curves among variables. Median age was 48 years (19-64 y). Among those patients who had cytogenetic data (28 patient, 70%), 12 (30%) were in high-risk category. Median time from diagnosis to allo-HCT was 6.5 months (2-54 months). Median follow-up period for living patients was 419 days (105-857). Pretransplant disease status was as follows; 24 patients (60%) in CR1, 12 patients (30%) in CR2 and 4 patients (10%) had active disease. The conditioning regimens for allo-SCT consisted of myeloablative (Bu16-CY120) (n=32, 80%) or reduced-intensity regimens (Flu150-Bu8)(n=8, 20%). Donors were HLA-matched siblings for 32 patients (80%), unrelated for 7 patients (17.5%) and haploidentical for 1 patient (2.5%). All but 2 patients (95%) received peripheral blood stem cells. All patients received primary antifungal prophylaxis. Overall, TRM at day 30 and 100 were 7.5% (n=3) and 10% (n=4), respectively. Late death (>100 days) was observed in 7 patients (17.5%) and 3 of them were related to allo-SCT. Grade 2-4 aGVHD was seen in 20 (50%) patients and chronic extensive GVHD in 8 patients (20%). Of those 24 patients who underwent allo-HCT in CR1, 18 patients (75%) were still in remission without any sign of disease. Nine of 16 patients (56.3%) who underwent allo-SCT beyond CR1 lost due to relapsed leukemia. Survival analysis revealed superior OS between patients in CR1 (median 901 days) and beyond CR1 (median 202 days) (log-rank, OS p=0.003). For disease free survival we have seen the same profile (p=0.007) (Fig 1 and 2). In CR1 patients (n=24) univariate analysis revealed no impact of standard-risk cytogenetics, high HCT-CI (³2), high WBC at dx (>30k), sex (F to M), ABO mismatch and double induction for CR achievement. The only adverse factor for short OS in CR1 was past history of invasive fungal infection pre allo-SCT (p=0.038, 901d vs 553d)(Fig 1). Allogeneic HCT in AML patients should be undertaken in CR1 with matched sibling donor. Pre-tx invasive fungal infection was the only worst predictive factor for OS in CR1 AML patients cohort.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.