REDUCED-INTENSITY TRANSPLANTATION AS A PART OF STANDARD TREATMENT STRATEGY IN PATIENTS AGED 60 TO 70 YEARS WITH ACUTE MYELOID LEUKEMIA – SINGLE CENTRE EXPERIENCE

Background

outcome of patients (pts) over 60 years of age with acute myeloid leukemia (AML) treated only with intensive chemotherapy is poor. To improve treatment results reduced-intensity transplantation (RIT) was establish as a part of standard treatment strategy for pts aged 60 to70 years with AML (except of pts with prognostically favourable AML) in our centre from 2003.

Aims

With the aim to evaluate transplant feasibility and the role of RIT in the treatment of pts aged 60 to 70 years with AML we analysed outcome of such pts in our centre from 2003.

Methods

from 1/2003 to 11/2014 AML was diagnosed in 188 pts aged 60 to 70 years. 120 pts were intensively treated and 61 pts with median of age 63 years (range, 60-68 years) with AML in 1^st CR (35 pts), in 2^nd CR (5pts), with primarily resistant AML (9 pts) and with AML beyond CR (12 pts) underwent RIT (30% HLA identical related, 41% HLA matched unrelated, 26% HLA mismatched unrelated, 3% haploidentical related). Source of stem cells was in 85% peripheral blood and in 15% bone marrow with the median of infused CD 34+ cells 4,8x10^6/kg (range, 1,7-14,9x10^6/kg). The conditioning regimen consisted of fludarabine (30mg/m2 for 4 days) and melphalan (140mg/m2 for 1 day), in 14 pts with ATG (ATG Fresenius 15mg/kg). CsA and methotrexate were used as GVHD prophylaxis except haploidentical RIT where posttransplant CPA and combination of CsA and MMF was used.

Results

the main reasons of impossibility to implement RIT in treatment of older pts with AML were death during remission induction treatment (39%), resistant or progressive AML (24%), non-availability of donor (16%), severe comorbidities (12%) and refusal of RIT (9%). However 51% of intensively treated pts with AML eventually underwent RIT. All pts fully engrafted and achieved complete remission (CR). 37 pts (60%) developed aGVHD (6 pts grade III-IV) and among 50 evaluable pts 22 (44%) of them developed chGVHD (9 limited, 13 extensive). With median follow-up 46 months (range, 4-123 months) 27 pts (44%) are alive (26 pts in CR). 14 pts (23%) relapsed and 13 of them died. 21 pts (34%) died due to NRM, 2 (3%) of them till day 100 after RIT and 11 (18%) of them till day 365 after RIT. The estimated probabilities of 3-years EFS and OS are 44% and 47%. 3-years OS for all intensively treated elderly pts was 38%.

Summary

our data show that half of intensively treated pts aged 60 to 70 years with AML were able to undergo RIT and that RIT even in case of unrelated or HLA mismatched donor is associated with acceptable NRM and encouraging disease control of unfavourable AML (3-years OS 47%). The relatively high percentage of transplanted pts undoubtedly influenced the overall results of the group of intensively treated elderly patients with AML with a median survival of 15 months and estimated 3-year OS of 38%. RIT should be considered as standard treatment option for consolidation therapy in elderly patients with AML.

Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, Elderly

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