Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-alpha for relapsed malignancy after allogeneic bone marrow transplantation.
BACKGROUND
Interferon-alpha (IFN) is known to promote graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo BMT). This property may also be used to enhance a graft-versus-leukaemia effect (GVL) after donor leucocyte infusion (DLI), a mode of therapy increasingly offered to patients relapsing after allo BMT.


OBJECTIVE
The aims of the present study were to examine the efficacy and toxicity of IFN therapy administered after granulocyte colony-stimulating factor (G-CSF)-stimulated blood cells given as DLI in patients with acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL), acute undifferentiated leukaemia (AUL) and multiple myeloma relapsing after allo BMT.


METHODS
Between October 1996 and September 1999, 27 patients (16 AML, four ALL, three CML, three multiple myeloma, one AUL) who relapsed after allo BMT were treated with chemotherapy followed by DLI, collected after G-CSF stimulation in all but two cases. Subsequently, IFN was given to patients without significant GVHD or rapidly progressive disease. The outcome after DLI with regard to remission rate, disease-free survival and GVHD was analysed.


RESULTS
Eighteen patients received IFN following DLI, 14 of whom developed significant GVHD (grade II-IV acute or extensive chronic); thereafter, GVHD resolved with cessation of IFN alone in four patients, but 10 required systemic immunosuppression. Twenty-three patients were given chemotherapy and DLI as initial treatment of relapse; 10 achieved complete remission (CR), in four patients this was only after the onset of GVHD. The other four patients received chemotherapy and DLI as a consolidation of a chemotherapy-induced remission. The CR was durable only in patients with CML (3 of 3) and AML (4 of 8).


CONCLUSIONS
Treatment with IFN induced GVHD in the majority of patients receiving DLI. The induction of GVHD and GVL by this approach produced excellent results in patients with CML and modest results in AML, but appeared to be less effective in myeloma and ALL.
Grigg
A
A
Department of Clinical Haernatology and Medical Oncology, Royal Melbourne Hospital, Victoria, Australia. andrew.grigg@mh.org.au
Kannan
K
K
Schwarer
A P
AP
Spencer
A
A
Szer
J
J
D000208:Acute Disease; D000328:Adult; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007938:Leukemia / Q000188:drug therapy / Q000628:therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000628:therapy; D017708:Leukocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000209:etiology; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
D016898:Interferon-alpha; D016179:Granulocyte Colony-Stimulating Factor