Lymphocyte depletion during treatment with intensive chemotherapy for cancer.
Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens.
Mackall
C L
CL
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Fleisher
T A
TA
Brown
M R
MR
Magrath
I T
IT
Shad
A T
AT
Horowitz
M E
ME
Wexler
L H
LH
Adde
M A
MA
McClure
L L
LL
Gress
R E
RE
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D009894:Opportunistic Infections / Q000276:immunology; D013997:Time Factors
D000970:Antineoplastic Agents; D003520:Cyclophosphamide