Internal tandem duplication (ITD) mutations affecting the juxtamembrane domain of the tyrosine receptor kinase, fms-like tyrosine kinase 3 (FLT3), have been reported in approximately 20% to 30% of all patients with acute myeloid leukemia (AML). FLT3-ITD mutations have been identified as the most significant prognostic factor in predicting relapse and poor overall survival. Duration of CR is usually shorter, relapse rates are higher, and the median OS is shorter with conventional chemotherapy. Here, we report the results of a analysis on the impact of allo-HCT in 124 patients with FLT3-ITD.

Method: We performed a review of the clinical data from December 2004 to May 2008 on all 82 FLT3/ITD positive AML patients. All of patients harbored an FLT3/ITD mutation at diagnosis. Of all patients,male were 51,female 31,median age was 26.5 years old(range 2~62 yrs). Among of patients, unrelated donor transplant were 16 cases, haplo-SCT 48, sibling matched 18cases. Complete remission before transplant were 55 cases, non-remission 27cases. Conditioning regimen were 3 patients used TBI/Cy, others 79 patients were Bu/Cy. Graft-versus-host disease (GVHD) prophylaxis was CsA, MMF and short-MTX. Stem cell source were 64 from bone marrow plus PBSC,18 from PBSC. Median number of MNC cells infusion were 8.0*10E8/kg(range 4.2~16.8), the CD34 positive cells were 4.2*10E6/kg (range 2.4~10.6).Except 1 case death during conditioning,the reming 81 cases patients were fully engrafted at the first month post transplantation by bone marrow puncture. The median days of WBC engraft was 14 days (10-21days), while the median days of platelet engraftment was 13 days (6-45days).

Results: The median fellow-up duration was 13.2 months(range 1-42months). Death were 18 patients, among of these relapse were 7 cases, one case achieved 2nd remission after DLI and had a EFS. Non-relapse mortality was 12 cases(including infection/sepsis 8,organ failure 4). EFS of all patients was 78%(graph1). There was no difference in EFS between haplo-SCT and matched SCT(including sibling and unrelated)(77.1% vs 79.4%, graph2), between CR and NR before transplant(80.0% vs 74.1%, graph 3). Acute GVHD I-II was 29.2%(24 cases),III-IV 4.8% (4 cases). Acute GVHD in haplo-SCT was higher than sibling/unrelated matched(45.8% vs 17.6%), Relapse rate was 8.5%. Hemorrhagic cystitis was 28%(23 cases).CMV viremia was 32.9%(27cases) and EBV viremia7.3%(6 cases).

Conclusion: AML with FLT3/ITD mutation has poor prognosis and OS,but these patients who received allo-HSCT have a good EFS and OS,and there were no difference between haplo-SCT and sibling/unrelated matched-SCT. There was no difference between CR and NR before transplant. But the median follow-up duration is shor,we need a long-term observation. Administration of FLT3 inhibitors before or after alloHCT might further improve future outcome of patients with FLT3-ITD leukemia.

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Disclosures

No relevant conflicts of interest to declare.

Topics:
allogeneic stem cell transplant, impedance threshold device, leukemia, myelocytic, acute, ms-like tyrosine kinase 3, transplantation, allopurinol, disease remission, graft-versus-host disease, graft-versus-host disease, acute, cd34 antigens

Author notes

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Asterisk with author names denotes non-ASH members.

© 2017 by The American Society of Hematology
2017
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