Graft versus host disease in autologous stem cell transplantation.
Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT). Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT. Eighty patients with several diagnostics were submitted to ASCT. After stem cell infusion, patients randomised in 4 groups. Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF. Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT. GVHD was positive in 23 patients (13 from group A and 10 from group B). All cases were grades I and II. A majority of CD4+ T lymphocytes was seen in skin infiltrates. No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups. With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others. However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05). We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.). Development of GVHD showed a better outcome for patients in our study except for those patients with MM. This results must be confirmed by a longer follow up of our patients and further studies.
Marin
G H
GH
Catedra de Farmacologia, Facultad de Medicina, Universidad Nacional de La Plata, Argentina.
Porto
A
A
Prates
V
V
Napal
J
J
Etchegogen
O
O
Rubens
L
L
Bordone
J
J
Castelletto
R
R
Buschiazzo
H
H
Morales
V
V
Milone
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous / Q000009:adverse effects
D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine