T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications.
Fourteen patients with T-cell-derived leukemia and lymphoma underwent high-dose chemoradiotherapy and anti-T-cell monoclonal antibody-treated autologous bone marrow transplantation (ABMT). All patients were either in sensitive relapse or had adverse prognostic features, and five patients had a history of bone marrow involvement with disease. Patients received a median of 2 (1 to 3) prior chemotherapy regimens; 10 patients received local radiotherapy. After high-dose ablative therapy, greater than 500/mm3 granulocytes and greater than 20,000 untransfused platelets/mm3 were noted at a median of 23 (13 to 48) and 26 (15 to 43) days post-ABMT, respectively. Natural killer (NK) cells, T cells (predominantly T8+), and monocytes were noted within the first 1 to 2 months post-AMBT, as seen in other series. Disease-free survival was a median of 10.1 months, 5.9 months for patients with T acute lymphoblastic leukemia or lymphoblastic lymphoma and 25.6 months for patients with T non-Hodgkin's lymphoma (NHL). Toxicities were common and severe. Thirty-six percent of patients developed bacteremias early post-BMT. Late complications included a skin rash consistent with graft versus host disease; infections with Herpes zoster, hepatitis, and Pneumocystis carinii; and the development of Epstein-Barr virus associated lymphoproliferative syndrome. Our findings suggest that patients who have undergone T-depleted ABMT have a profound immunodeficiency not reflected in the phenotypic reconstitution of the T and NK cells. Characterization of the functional deficiency may facilitate the development of methods to reduce the long-term toxicity of AMBT in these patients.
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
K C
KC
Anderson
R
R
Soiffer
R
R
DeLage
T
T
Takvorian
A S
AS
Freedman
S L
SL
Rabinowe
L M
LM
Nadler
K
K
Dear
L
L
Heflin
P
P
Mauch
D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000473:pathology; D006505:Hepatitis / Q000209:etiology / Q000401:mortality / Q000473:pathology; D006562:Herpes Zoster / Q000209:etiology / Q000401:mortality / Q000473:pathology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011020:Pneumonia, Pneumocystis / Q000209:etiology / Q000401:mortality / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000276:immunology*
D003520:Cyclophosphamide