DONOR BUFFY COAT TRANSFUSIONS FOR ADOPTIVE IMMUNOTHERAPY IN HUMAN AND CANINE CHIMERAS

作者：KOLB HJ^*; BEISSER K; HOLLER E; MITTERMULLER J; CLEMM C; WALTHER U; SCHUMM M; LEDDEROSE G; WILMANNS W; THIERFELDER S

来源：Periodicum Biologorum, 1991, 93(1): 89-96.

Recurrent leukemia after marrow transplantation indicates a very poor prognosis. Three patients were treated with interferon-alpha (IFN-alpha) and buffy coat transfusions from their marrow donor for hematologic relapse of chronic myelogenous leukemia (CML) 2 and 3 years after transplantation. Complete hematologic and cytogenetic remissions were induced. Two patients developed graft-versus-host disease (GVHD) requiring transient immunosuppresion, one remained free of signs of GVHD. Remissions are sustained for 14, 18 and 25 months, respectively, without further antileukemic treatment. As a model of adoptive imunotherapy mixed chimerism and GVH-tolerance was induced in DLA-identical canine littermates followed by buffy coat transfusions from the marrow donor at various times after transplantation. Stable mixed chimerism was achieved by the use of graded numbers of marrow cells and treatment of the marrow with absorbed ATG for prophylaxis of GVHD. Chimerism was mized in 2 and complete in 1 dog given 2.0 x 10(8) MNC/kg. It was mixed in 1 dog given 1.5 x 10(8) MNC/kg and in 3 dogs given 1.0 x 10(8) MNC/kg, whereas 2 dogs given 1.0 x 10(8) MNC/kg, became reversals. Clinically significant GVHD did not develop. Donor buffy coat was transfused on days 1 and 2, 21 and 22, or 61 and 62 after transplantation in 2 dogs, respectively. Dogs given buffy coat on days 1 and 2, or 21 and 22 died of GVHD. Transfusions on days 61 and 62 did not induce GVHD. The proportion of donor type cells increased in dogs given buffy coat. The results indicate that transfusions of donor buffy coat into tolerant chimeras inactive CML of host type and improve chimerism without necessarily inducing severe GVHD.

• 出版日期1991-4