INFUSION OF HLA-MISMATCHED PERIPHERAL BLOOD STEM CELLS DURING TREATMENT AML IN ELDERLY PATIENTS

ABSSUB-4257

Background: The treatment of the elderly patients with AML still remains unsatisfactory. The reasons for the poor prognosis in elderly patients are the unfavorable biology of AML, incidence of relevant comorbidities and increased risk of chemotherapy-related mortality. In 2011 Mei Guo et al. published a study showing optimistic outcomes in treatment of the elderly AML patients with chemotherapy followed by infusion of HLA-mismatched peripheral blood stem cells. However, other studies confirming these results are lacking.

Aims: To prove efficacy, feasibility and safety of the treatment published in the study by Mei Guo et al.. The preliminary results are presented below.

Methods: Only the patients with de novo and secondary AML aged 60-70 were eligible for the study. Remission induction chemotherapy consisted of Ara-C 100mg/m2 daily for 7 days and daunorubicin 90 or 45mg/m2 daily for 3 days followed by the infusion of G-CSF-mobilized HLA-mismatched donor peripheral-blood stem cells 24 hours after the end of the chemotherapy. Bone marrow assessment was performed at day 15 and after hematological recovery. Patients with CR received 2 consolidations with Ara-C 1g/m2 given every 12 hours on days 1, 3 and 5 followed by the infusion of HLA-mismatched peripheral-blood stem cells 24 hours after the end of the chemotherapy. The donors of 7/8 patients were HLA haploidentical children, in case of the eighth patient, the donor was HLA haploidentical sibling. Donor microchimerism was detected in peripheral leucocytes using a real-time quantitative PCR protocol and was measured 7, 14 and 21 days after the infusion of HLA-mismatched peripheral-blood stem cells.

Results: Between 1/2013-12/2013 eight patients with median age of 65 years (60-70) were treated according to this protocol. The median follow up was 6.8 months. After induction 3/8 patients achieved CR, the other 5/8 did not and were excluded from the study. All 3 patients who achieved CR received both cycles of consolidation chemotherapy. The OS at 6 months and EFS at 6 months were 37% and 37% respectively. Two of three patients with treatment response relapsed during the first year after achieving CR. Thus only one patient is still in long term CR. All patients presented with hematological toxicity gr. 3 or more. Non-hematological toxicities gr. 3 and higher were: febrile neutropenia – 7/8, supraventricular arrhythmia – 2/8, 1/8 patient developed anti HLA antibodies, with refractoriness to platelet transfusion. Only 2 of 8 patients presented after induction with donor microchimerism at day 7 and 0/8 at day 14 and 21. Post-consolidation measurements revealed only autologous recovery in all of the three patients.

Summary/Conclusion: Our (even preliminary) results did not prove the efficacy of previously published approach, while except one, all patients did not responded or early relapsed.

Keywords: Acute myeloid leukemia, Elderly, HLA mismatched

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