B. Glass et al., ALLOGENEIC PERIPHERAL-BLOOD PROGENITOR CELLS FOR TREATMENT OF RELAPSEAFTER BONE-MARROW TRANSPLANTATION, Bone marrow transplantation, 20(7), 1997, pp. 533-541
Donor leukocyte infusions (DLI) are an effective therapy for patients
who relapse with leukemia after bone marrow transplantation (BMT). Sev
ere graft-versus-host disease and prolonged periods of pancytopenia co
mpromise the success of this treatment in a substantial number of pati
ents. We used filgrastim-mobilized peripheral blood progenitor cells (
PBPCs), in some cases preceded by cytoreductive therapy, to circumvent
some of the problems associated with DLI. Eleven patients (median age
41 years) received a total of 20 donor cell infusions. Their diagnosi
s was CML in hematological (two patients) or cytogenetic relapse (two
patients), six patients suffered from acute myeloid leukemia (AM; n =
5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (A
LL Ph+). One patient had multiple myeloma (MM). All six patients with
acute leukemias received cytoreductive therapy prior to PBPC infusions
; three patients with CML were pretreated with IFN alpha. Four of four
patients with CML responded to PBPC infusions and currently are in co
mplete clinical and molecular remission for time periods between 1 and
12 months. Six of six patients with acute leukemias achieved a comple
te remission. All of them relapsed after a median remission duration o
f 24 weeks (range 11-49 weeks). Three patients relapsed at extramedull
ary sites (CNS, testes, skin). Four of six acute leukemia patients rec
eived further cytoreductive therapy. All patients responded again and
are in complete remission far time periods between 14 and 615 days. Tw
o patients with acute leukemias have died due to dissemination of the
disease. The patient with MM did not respond and is alive with disease
. Severe (grade III) acute GVHD developed in two of 11 patients, three
patients developed grade II disease, six patients did not show any si
gns of GVHD. Extensive chronic GVHD has developed in two cases to date
. Patients with chemotherapy prior to PBPC infusion developed neutrope
nia and thrombocytopenia with a maximum duration of 20 and 14 days, re
spectively; prolonged periods of neutropenia did not occur. Two patien
ts developed long-lasting thrombocytopenia in spite of PBPC infusion,
in one case followed by leukemic relapse. Repeated courses of chemothe
rapy and PBPC infusion were generally tolerated well; no early deaths
due to treatment-related toxicity or GVHD were observed. We conclude t
hat the use of allogeneic PBPC instead of DLI in patients with relapse
after BMT is technically feasible and safe. The efficacy of PBPC infu
sions seems comparable to DLI in patients with CML. Patients with acut
e leukemias also achieved complete albeit transient remissions. Aggres
sive chemotherapy followed by PBPC infusions resulted in only limited
duration of cytopenia. The usage of PBPC infusion instead of non G-CSF
-mobilized donor cells for treatment of relapse after BMT may reduce p
ancytopenia-related complications and merits further investigation.