Efficiency Of 7+3 Chemotherapy Followed By Donor Lymphocyte Infusion In Patients With Relapsed Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
Authors: Bogdanov Rashit , Mendeleeva Larisa , Parovichnikova Elena , Kuzmina Larisa , Galtseva Irina , Savchenko Valeri G. 
Published: October 2019

Relapses after allogeneic stem cell transplantation (allo-SCT) are the main cause of treatment failure in acute myeloid leukemia (AML). Chemotherapy with subsequent donor lymphocyte infusions (DLI) is considered to be the optimal approach for complete remission (CR) achievement and induction of “graft versus leukemia” effect. There is a tendency to use low-dose chemotherapy (i.e. Low-dose Ara-C) in this setting because of less toxicity. However the efficacy of low-dose chemotherapy is not satisfactory and leads to 45-67% CR rate. In this study we apply intensive chemotherapy (7+3) followed by DLI in aplasia in with relapsed AML.

Aim
To investigate the efficacy of DLI perfomed in neutropenia after reinduction chemotherapy 7 +3 (Cytarabine 100 mg/m^2 every 12 hours daily for 7 days, and Idarubicin 12 mg/m^2 daily on days 1, 2, and 3) in AML patients (pts) with overt relapse after allo-SCT.

Methods
The study comprised 16 AML patients. The median age was 31 years (16 - 57 years), male – 11 female - 5. Twelve patients underwent allo-SCT in first remission, 4 pts - in overt relapse of AML. Allo-SCT was carried out from HLA-matched sibling donor in all pts. Myeloablative conditioning regimen was performed in 10 pts. Reduced intensity conditioning (RIC) - in 6 pts. AML relapse occurred at a median 4,7 months (range from 1 to 51 months) after allo-SCT.
Patients received DLI at day 7 (7-14 days) after chemotherapy during myelotoxic agranulocytosis. The number of infusions ranged from 1 to 4 (median 2 DLI) per patient. DLI after chemotherapy were carried out twice in 1 patient due to the second relapse. So we analysed 17 cases of relapse in 16 pts.
Total amount of the CD3+cells varied from 1 to 16,7x10^7 CD3+cells/kg (median 6,0x10^7 CD3+ cells/kg). The interval between DLI was 1-4 weeks. All pts received 2 - 6 MUE Interleukin-2 (IL-2) subsequently after DLI.
Chimerism was monitored by PCR analysis (VTTR and STR) and by FISH – analysis for centromers of X and Y – chromosomes after DLI each 2-4 weeks up to 6 months, then every 3 months.

Results
Complete remission with 100% donor chimerism was achieved in 14 (82%) out of the 17 cases. There were no toxic deaths, 3 pts died in leukemia progression. All pts developed severe infections in neutropenic phase (mucositis, pneumonia, sepsis), but they were cured.
Eight pts (57%) out of 14 developed a relapse in 5 months after DLI (from 1 to 17 months) and 6 pts (35%) remained in remission. Follow-up period was 12 months (1 - 124 months). Median overall survival constituted 15 months.
Acute graft versus host disease (GVHD) after DLI was diagnosed in 8 patients 47% (6 - I-II grade; 2 - III-IV grade). Chronic GVHD was diagnosed in 8 pts (47%): limited -6 pts (35%), extensive - 2 pts (12%).

Conclusion
Our data show that despite myelotoxicity and infections 7+3 and subsequent DLI+ IL-2 is an effective treatment for AML pts with overt relapse after allo-SCT.

Disclosures:
No relevant conflicts of interest to declare.