Graft-versus-host disease is associated with a lower relapse incidence after hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.
To determine the graft-versus-leukemia effect after hematopoietic stem cell transplantation (HSCT), we studied 199 patients with acute lymphoblastic leukemia who underwent transplantation at Huddinge University Hospital between 1981 and 2001. Seventy-four patients were in first complete remission (CR1), and 125 were in later stages of the disease. Most patients had an HLA-identical sibling donor. Conditioning consisted mainly of total body irradiation and cyclophosphamide, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Acute GVHD developed in 143 patients and chronic GVHD in 67. The 5-year probability of relapse and relapse-free survival (RFS) were 32% and 49%, respectively, in patients in CR1, as compared with 53% and 33% in those with more advanced disease. In the multivariate risk factor analysis of relapse, we found that the absence of chronic GVHD (P<.001), absence of herpes simplex virus infection after HSCT (P=.003), combination prophylaxis with methotrexate and cyclosporine (P=.01), and >6 weeks from the diagnosis to CR (P=.025) were independent risk factors for relapse after HSCT. Factors associated with a better relapse-free survival were chronic GVHD (P<.001), ABO blood group mismatch (P=.006), younger patient age (P=.01), and an HLA-matched donor (P=.01). The association between herpes simplex virus infection and a low frequency of relapse is a new observation and may indicate that viral antigens play a role in the induction of an antileukemic effect.
Center for Allogenic Stem Cell Transplantation and Department of Clinical Immunology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Anna
A
Nordlander
Jonas
J
Mattsson
Olle
O
Ringdén
Katarina
K
Leblanc
Britt
B
Gustafsson
Per
P
Ljungman
Petter
P
Svenberg
Johan
J
Svennilson
Mats
M
Remberger
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D017893:Photopheresis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000628:therapy*; D012008:Recurrence
D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents