Risk Factors of HLA-Haploidentical Transplantation Using the Combination of Unmodified Marrow and CD6-Depleted G-CSF Mobilized Blood Cells.

Allogeneic stem cell transplantation from HLA-haploidentical family members has been studied in 80 patients for the treatment of hematological malignancies in advanced stages. The protocol involves unmodified marrow on day 0 and CD6-depleted G-CSF-mobilized blood cells on day 6. Engraftment was seen in patients treated with myeloablative (12 Gy) and non-myeloablative (4 Gy) doses of total body irradiation. Graft-versus-host disease (GVHD) was mild or absent in 53% and severe GVHD did not develop after changing to a more effective method of depletion of CD6-positive cells. Acute GVHD resolved more often and chronic GVHD was less severe than in HLA-identical sibling transplantation. Here we evaluated survival and relapse risk. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was the diagnosis in 41 patients, acute lymphoid leukemia (ALL) in 19 patients, chronic myelogenous leukemia (CML) in 2, chronic lymphocytic leukemia (CLL) in 3, high grade lymphoma (NHL) in 14 and severe aplastic anemia (SAA) in one patient. The patient’s age ranged from 17 to 62 years (median 36.5 yrs), for 65 patients a relative of first degree and for 15 patients a second degree relative was the donor. The major cause of death was recurrence of the disease (29 pts.), 7 patients died early and 22 pts. died of complications (infections 12, GVHD 3, pulmonary compl. 2, PTLD 3, cerebr. hemorrhage 1, liver tox. 1). Survival was significantly better in male patients with female donors (2 yr survival 36% vs 13%; p=0.001), patients transplanted with cells from their mother rather than from the father (2 yr survival 55% vs 8%; p=0.02) and patients transplanted in an earlier phase (2yr survival 50% vs 15%; p=0.048). Patients transplanted for ALL (2 yr. survival 31%) fared better than patients with AML/MDS (2yr survival 23%)and patients with NHL (2 yr. survival 12.5%) (p=0.08). Age, number and type of HLA-mismatches, as well as the depletion method had no effect on survival and on relapse risk. The favorable effect of the female gender of the donor on survival was still significant in multivariate analysis after adjustment for the stage of the disease and the diagnosis (p=0.01). The possibility of non-inherited maternal antigens (NIMA) inducing tolerance was tested in siblings sharing the paternal haplotype. There was a weak effect in the host-versus-graft direction (p=0.06), but no effect in the graft-versus-host direction. The risk of relapse was lowest in patients transplanted with stem cells from their mother as compared to those transplanted from their father (p=0.002). Female gender of the donor was favorable even in patients without GVHD. In summary female donors are preferable to male donors for control of leukemia and survival.