Similar Outcomes of Allogeneic Hematopoietic Cell Transplantation from Matched Sibling Donor and Haploidentical Donor for Refractory/Relapsed Acute Myeloid Leukemia
Authors: Liu Dai-Hong , Yu Li , Huang Wenrong , Dou Liping , Li Honghua , Chunji Gao , Jian Bo , Li Fei , Wang Lili 
Published: October 2019

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only effective, even curative treatment for refractory/relapsed AML patients. Unmanipulated haploidentical HCT (haplo-HCT) resulted in encouraging outcomes for treatment of hematologic malignancies and become an alternative option in case of lacking HLA matched sibling donor (MSD). Unmanipulated haplo-HCT from G-CSF mobilized bone marrow and peripheral blood stem cell (PBSC) has shown similar results as that from MSD-HCT in leukemia. Here, we report the results of a cohort study on the efficacy and toxicity of haplo-PBSCT compared with MSD-PBSCT for treatment of refractory/relapsed AML.

PATIENTS AND METHODS

Among 419 newly diagnosed AML patients, 69 patients relapsed during CR1 and were planned to receive allo-HCT after re-induction. The order of preference of donors was MSD, matched unrelated (HLA 10/10 or 9/10 loci matched), or haploidentical donor. Thirty patients received haplo-PBSCT and 13 patients MSD-HCT (July, 2007 ~ June, 2014) at our unit. There was no difference of the characteristics of demography, disease or transplantation between these two groups (Table 1).

High-resolution DNA techniques were used to evaluate the HLA-A, B, DRB1, DQB1, and C loci. Donors were treated with rhG-CSF (5 mg.kg-1.day-1) for consecutive days. The PBSCs were collected on day 5 - 6 and infused on the day of collection.

The conditioning regimen consisted of Bu (9.6 mg.kg-1, intravenously, days -10 ~ -8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7 ~ -6), CY (120 mg kg-1, days -4 ~ -3), and ATG (rabbit; 10 mg.kg-1, days -5 ~ -2). MSD-HCT patients had the same conditioning regimen without ATG. All transplant recipients received cyclosporine A, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. The endpoint of the last follow-up for all surviving patients was June 30, 2015.

RESULTS

Sustained myeloid engraftment with full donor chimerism was achieved in both groups (100%) at a median of 16 (10 - 26) days. Twenty-six patients (86.7%) in haplo-PBSCT group and all patients in MSD-PBSCT group achieved platelet recovery. There was no difference of the cumulative incidence of acute GVHD grade 2-4 (Fig. 1), chronic GVHD (20% vs 33.3%, P=0.581), transplantation-related mortality (TRM) (16.7% vs 0%, P = 0.121), relapse (33.3% vs 38.5%, P = 0.578, Fig 2) between haplo-PBSCT and MSD-PBSCT group. Donor age of 41yr and older was an independent risk factor for inferior leukemia-free-survival (27.8% vs 37.2%, P = 0.004).

CONCLUSION

In this cohort study, haplo-PBSCT showed similar outcomes in patients with refractory/relapsed AML compared with MSD-PBSCT. It suggested the feasibility of G-CSF-primed PBSC as a graft source in unmanipulated haplo-HCT under myeloablative conditioning, which was effective and tolerable for treatment of poor risk leukemia.

Table 1. Characteristics of patients and donors Haploidentical donor Matched sibling donor P value Cases % Cases % Gender, n (%) Receipt Male 22 73.3 8 61.5 0.485 Donor Male 22 73.3 7 53.8 0.292 Age,y, median(range) Patient ≤40 y, n (%) 21 70 6 46.2 0.178 Donor ≤41 y, n (%) 13 43.3 5 38.5 1.000 AML, n (%) 1.000 CR2 5 16.7 2 15.4 NR/beyond CR2 25 83.3 11 84.6 Time to transp 0.51 ≥7m 14 46.7 8 61.5 Conditioning Regimen, n (%) 0.675 BuCy 22 73.2 9 69.2 TBIcy 4 13.3 1 7.7 FB 4 13.3 3 23.1 CD34+ in graft (106/kg) 0.499 ≥4.77 17 56.7 5 41.7

Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3.

Disclosures

No relevant conflicts of interest to declare.