Similar Incidence of Severe Acute Gvhd and Less Extensive Chronic Gvhd in PBSCT from Unmanipulated Haploidentical Donor Compared with That from Matched Sibling Donor for Patients with Hematologic Malignancies

Abstract

▪Unmanipulated haploidentical hematopoietic stem cell transplantation (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). Transplantation with G-CSF mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with MSD. Unmanipulated haploidentical donor (haplo-PBSCT) has been applied in patients with hematologic malignancies. However, the characteristics of graft-versus-host disease (GVHD) in unmanipulated haplo-PBSCT are not clear. Here, we report the results of a cohort study on the clinical features of acute and chronic GVHD in haplo-PBSCT compared with PBSCT from MSD in patients with hematologic malignancies.PATIENTS AND METHODSBetween July, 2007 and June, 2014, 94 patients with hematologic malignancies received haplo-PBSCT and 100 patients received PBSCT from MSD consecutively at our unit (Table 1). The PBSCs were collected on day 5 and 6 after 4 days of rhG-CSF (5 mg.kg¨C1 °¤day¨C1), then were infused on the day of collection. The conditioning regimen consisted of Bu (9.6 mg.kg-1, iv, days -10~-8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7~-6), CY (120mg kg-1, days -4~-3). Antithymoglobulin (ATG, rabbit; 10 mg.kg-1, days -5~-2) was used for haplo-PBSCT. All 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 July 15, 2015.RESULTSAmong the patients with acute GVHD, there was no difference of the rate of the involved organs between these two groups (skin: 67.4% vs 68.0%, p=1.000; liver: 15.2% vs 20.0%, p=0.742; gut: 33.3% vs 32%, p=1.000). Haplo-PBSCT was associated with higher incidence of acute GVHD grade 2-4 (HR: 3.04, 95% CI: 1.55-5.98, P =0.001) and lower incidence of extensive chronic GVHD (HR: 0.49, 95% CI: 0.24-0.99, P =0.047) compared with MSD PBSCT. There was no difference of the incidence of acute GVHD grade 3-4 between these two groups (haplo-PBSCT, 9.6% vs MSD PBSCT 8.9%, P =1.000). According to NIH criteria, the incidence of severe chronic GVHD was lower in haploidentical group (13.6%) compared with MSD group (40.5%, p=0.041). There was no difference of those for mild and moderate chronic GVHD (mild: 27.3% vs 13.5%, p=0.189; moderate: 59.1% vs 45.9%, p=0.422).CONCLUSIONIn this cohort study, haplo-PBSCT was associated with similar incidence of severe acute GVHD, lower extensive chronic GVHD and lower severe chronic GVHD compared with MSD-PBSCT. It suggested the potential advantage of ATG in improvement of long-term quality of life of the transplant recipients.Table 1Characteristics of patients and donorsHaploidentical donor, n = 94Matched sibling donor, n = 100P valueGender, n (%)Receipt, male73 (77.7)64 (64.0)0.041Donor, male63 (67.0)60 (60.0)0.371AgePatient, y, median27380.055Donor, y, median38390.364Hematologic malignances, n (%)Acute leukemia72 (76.6)61 (61.0)MDS3 (3.2)21 (21.0)0.000CML5 (5.3)10 (10.0)Lymphoma14 (14.9)8 (8.0)Status of disease, n (%)0.000CR142 (44.7)76 (76)CR214 (14.9)5 (5)NR/beyond CR238 (40.4)19 (19)Time to transplant (d)3612990.946Conditioning Regimen, n (%)0.354BuCy60 (63.8)66 (66.0)TBIcy28 (29.8)23 (23.0)FB6 (6.4)11 (11.0)CD34+ in graft (106/kg)5.864.770.057≥4.6051 (54.3)41 (41.0)0.084 DisclosuresNo relevant conflicts of interest to declare.