Autologous transplantation of bone marrow purged in vitro with anti-CD7-
(WT1-) ricin A immunotoxin in T-cell lymphoblastic leukemia and lymphoma
FW Preijers, T De Witte, JM Wessels, GC De Gast, E Van Leeuwen, PJ Capel and C Haanen
Department of Hematology, University Hospital Nijmegen, The Netherlands.
Seven patients with high-risk acute T-cell lymphoblastic leukemia (T- ALL)
and six with T cell lymphoma (T-LL) were treated with autologous bone
marrow transplantation (ABMT) after in vitro purging of their bone marrow
with WT1 (CD7)-ricin A-chain immunotoxin. CD7 expression on the tumor cells
showed large variations between the individual patients and was highly
related to the specific cytotoxicity of WT1-ricin A. Incubation of bone
marrow with up to 10(-8)mol/L WT1-ricin A in the presence of 6 mmol/L NH4Cl
did not compromise the growth potential of the hematopoietic progenitors
CFU-GM, CFU-GEMM, and BFU-E. Hematologic engraftment (greater than 10(9)
leukocytes/L) occurred within a normal time period (median, 17 days). Seven
patients are alive and in complete remission (CR) at 48+, 44+, 40+, 26+,
11+, 7+, and 6+ months after ABMT. Four patients relapsed within 6 months
after ABMT. Two of them had the lowest CD7 expression on their tumor cells,
the other two were transplanted in CR2 and CR3. Two patients died from
transplantation related infections. The immunologic reconstitution was
delayed, although the numbers of T cells reached normal levels within 1
month. The number of CD7+ cells remained low up to 1 year after
transplantation. The T4/T8-ratio was decreased for at least 6 months. The
T-cell response to mitogens recovered to normal levels after 1 year. This
study shows that ABMT with WT1-ricin A purged bone marrow in high-risk
T-cell malignancies results in a complete hematopoietic and a delayed
immunologic reconstitution. The actuarial relapse free survival is 61% at 3
years.
Volume 74,
Issue 3,
pp. 1152-1158,
08/15/1989
Copyright © 1989 by The American Society of Hematology
