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Treatment with recombinant interferon (alpha-2b) early after bone marrow
transplantation in patients at high risk for relapse [corrected] [published
erratum appears in Blood 1992 Jun 15;79(12):3397]
HG Klingemann, AP Grigg, K Wilkie-Boyd, MJ Barnett, AC Eaves, DE Reece, JD Shepherd and GL Phillips
Division of Hematology, Vancouver General Hospital, BC Canada.
Relapse continues to be a problem after bone marrow transplantation (BMT)
for hematologic malignancies, particularly in recipients of autologous or
T-cell-depleted allogeneic grafts and in patients with advanced disease.
Interferon (IFN) has shown antiproliferative activity in several malignant
hematologic diseases and potentially may be of benefit when administered
early after BMT when the number of residual cells is minimal. We tested in
a phase I study the maximum tolerated daily dose of recombinant IFN
alpha-2b in patients who had received a transplant for a disease at high
risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond
first remission, advanced myelodysplastic syndrome, acute lymphoblastic
leukemia at any stage, chronic myeloid leukemia in accelerated or blast
phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2
and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The
intention was to administer IFN as soon as stable engraftment after BMT was
achieved (defined as an absolute neutrophil count of greater than 2.0 x
10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive
days) and continued for 2 months. A total of 14 patients were enrolled
after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity
was myelosuppression. Significant (grade 2 to 4) neutropenia and
thrombocytopenia led to discontinuation or dose reduction in five of eight
patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate
(grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority
of patients independent of the IFN dose. De novo acute GVHD responsive to
steroid treatment developed in 3 of 11 allograft recipients. Natural killer
(NK) cell function was low before IFN treatment and was not improved with
the cytokine. Conversely, interleukin-2-activated NK cells showed normal
function even before starting IFN and no change was seen during IFN
treatment. Clonogenic hematopoietic progenitor studies showed depression of
all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid,
monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-
erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2.
Considering this result and the incidence and severity of marrow depression
seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the
maximum dose safely tolerated if IFN alpha-2b is administered in this
setting for a prolonged course on a daily basis.
Volume 78,
Issue 12,
pp. 3306-3311,
12/15/1991
Copyright © 1991 by The American Society of Hematology
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