Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF
U. Platzbecker et al., Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF, ANN HEMATOL, 80(3), 2001, pp. 144-149
Ten patients with high-risk acute myeloid leukemia (AML), chronic myeloid l
eukemia (CML), and myelodysplastic syndrome (MDS) relapsing early (<1 year,
n=8) or late (greater than or equal to1 year, n=2) after allogeneic transp
lantation were treated with cytoreductive chemotherapy followed by unmanipu
lated peripheral blood stem cell transplantation (PBSCT) from related (n=3)
and unrelated donors (n=7). In order to enhance the grart-versus-leukemia
effect, patients received no graft-versus-host disease (GVHD) prophylaxis a
nd granulocyte-macrophage colony-stimulating factor (GM-CSF) was given at a
dose of 60 mug/m(2) after transplant. Acute GVHD grade I-IV was seen in al
l patients. Eight out of ten patients achieved complete remission: one out
of two patients with AML and late relapse is in good condition with limited
chronic GVHD more than 1 year after the second PBSCT. The other patient di
ed on day +171 after the second PBSCT from cerebral aspergillosis. One pati
ent with blastic phase CML achieved molecular remission but died +330 days
after the second PBSCT because of intracranial bleeding. Of the remaining f
ive patients, three died of infectious complications on days +36, +70, and
+27, one patient died with extramedullary relapse on day +35, and one from
multi-organ failure in association with acute GVHD on day +32 after the sec
ond PBSCT. Two out of ten showed progressive disease and died on days +30 a
nd +90, respectively. Although several patients achieved complete remission
, the high risk of GVHD and treatment-related mortality should be kept in m
ind, especially when a second transplant is considered during a period of l
ess than 12 months after the first procedure. Monitoring of minimal residua
l disease might predict relapse thus preventing high doses of cytotoxic dru
gs for reconditioning. The potential of GM-CSF to enhance the graft-versus-
leukemia reactivity after cytoreductive therapy for allogeneic transplantat
ion warrants further investigation.