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

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 METHODS

Between 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.

RESULTS

Among 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).

CONCLUSION

In 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 1. Characteristics of patients and donors

	Haploidentical donor, n = 94		Matched sibling donor, n = 100		P value
Gender, n (%)
Receipt, male	73 (77.7)		64 (64.0)		0.041
Donor, male	63 (67.0)		60 (60.0)		0.371
Age
Patient, y, median	27		38		0.055
Donor, y, median	38		39		0.364
Hematologic malignances, n (%)
Acute leukemia	72 (76.6)		61 (61.0)
MDS	3 (3.2)		21 (21.0)		0.000
CML	5 (5.3)		10 (10.0)
Lymphoma	14 (14.9)		8 (8.0)
Status of disease, n (%)					0.000
CR1	42 (44.7)		76 (76)
CR2	14 (14.9)		5 (5)
NR/beyond CR2	38 (40.4)		19 (19)
Time to transplant (d)	361		299		0.946
Conditioning Regimen, n (%)					0.354
BuCy	60 (63.8)		66 (66.0)
TBIcy	28 (29.8)		23 (23.0)
FB	6 (6.4)		11 (11.0)
CD34+ in graft (106/kg)	5.86		4.77		0.057
≥4.60	51 (54.3)		41 (41.0)		0.084