Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia patients.
To determine if partial T cell depletion and intensive post-transplant immunosuppression is effective for the prevention of graft-versus-host disease (GVHD) in pediatric recipients of HLA-non-identical marrow transplants, 10 children with leukemia received high-dose thiotepa, cyclophosphamide and total body irradiation followed by transplantation of CD3-depleted marrow from matched unrelated or one-antigen mismatched related adult donors. To maximize the number of stem cells infused, a large volume (1-1.51) of marrow was harvested from the donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6) CD34+ cells/kg, 1.4 x 10(6) CD3+ cells/kg, and 1.6 x 10(6) CD5+ cells/kg as assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A chain immunotoxin (XZ-CD5) were used for prevention of GVHD post-transplant. All patients achieved an ANC > 0.5 x 10(9)/l. No patient developed capillary leak syndrome or renal failure from XZ-CD5. Five developed grade 2-4 acute GVHD, and all responded to treatment with steroids. Five of nine evaluable patients developed chronic GVHD. Two patients relapsed, but the most common cause of death was infection with or without chronic GVHD. Four patients survive 10+ to 27+ months post-transplant. XZ-CD5 is well-tolerated in T cell-depleted marrow transplant recipients. However, partial T cell depletion and intensive post-transplant immunosuppression did not prevent moderate acute GVHD or chronic GVHD. This may have been due to the high number of T cells infused with the marrow.
Przepiorka
D
D
Department of Hematology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Chan
K W
KW
Champlin
R E
RE
Culbert
S J
SJ
Petropoulos
D
D
Ippoliti
C
C
Khouri
I
I
Huh
Y O
YO
Vreisendorp
H
H
Deisseroth
A B
AB
D000293:Adolescent; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008297:Male; D012276:Ricin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000906:Antibodies; D017252:CD3 Complex; D018956:CD5 Antigens; D006680:HLA Antigens; D000922:Immunotoxins; D012276:Ricin