Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy

C. L. Mackall, T. A. Fleisher, M. R. Brown, M. P. Andrich, C. C. Chen, I. M. Feuerstein, M. E. Horowitz, I. T. Magrath, A. T. Shad, S. M. Steinberg, L. H. Wexler, R. E. Gress

Research output: Contribution to journalArticle

Abstract

Background. Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus- independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. Methods. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. Results. There was an inverse relation between the patients' ages and the CD4+ T- lymphocyte counts six months after therapy was completed (r=-0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r=0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P=0.015). Conclusions. Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalNew England Journal of Medicine
Volume332
Issue number3
DOIs
StatePublished - 1995
Externally publishedYes

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Regeneration
T-Lymphocytes
Drug Therapy
Thymus Gland
Lymphocytes
Virus Diseases
CD4 Lymphocyte Count
Bone Marrow Transplantation
Young Adult
Glycoproteins
Protein Isoforms
Bone Marrow
HIV
Therapeutics
Population
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mackall, C. L., Fleisher, T. A., Brown, M. R., Andrich, M. P., Chen, C. C., Feuerstein, I. M., ... Gress, R. E. (1995). Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. New England Journal of Medicine, 332(3), 143-149. https://doi.org/10.1056/NEJM199501193320303

Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. / Mackall, C. L.; Fleisher, T. A.; Brown, M. R.; Andrich, M. P.; Chen, C. C.; Feuerstein, I. M.; Horowitz, M. E.; Magrath, I. T.; Shad, A. T.; Steinberg, S. M.; Wexler, L. H.; Gress, R. E.

In: New England Journal of Medicine, Vol. 332, No. 3, 1995, p. 143-149.

Research output: Contribution to journalArticle

Mackall, CL, Fleisher, TA, Brown, MR, Andrich, MP, Chen, CC, Feuerstein, IM, Horowitz, ME, Magrath, IT, Shad, AT, Steinberg, SM, Wexler, LH & Gress, RE 1995, 'Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy', New England Journal of Medicine, vol. 332, no. 3, pp. 143-149. https://doi.org/10.1056/NEJM199501193320303
Mackall, C. L. ; Fleisher, T. A. ; Brown, M. R. ; Andrich, M. P. ; Chen, C. C. ; Feuerstein, I. M. ; Horowitz, M. E. ; Magrath, I. T. ; Shad, A. T. ; Steinberg, S. M. ; Wexler, L. H. ; Gress, R. E. / Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. In: New England Journal of Medicine. 1995 ; Vol. 332, No. 3. pp. 143-149.
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abstract = "Background. Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus- independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. Methods. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. Results. There was an inverse relation between the patients' ages and the CD4+ T- lymphocyte counts six months after therapy was completed (r=-0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r=0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P=0.015). Conclusions. Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.",
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T1 - Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy

AU - Mackall, C. L.

AU - Fleisher, T. A.

AU - Brown, M. R.

AU - Andrich, M. P.

AU - Chen, C. C.

AU - Feuerstein, I. M.

AU - Horowitz, M. E.

AU - Magrath, I. T.

AU - Shad, A. T.

AU - Steinberg, S. M.

AU - Wexler, L. H.

AU - Gress, R. E.

PY - 1995

Y1 - 1995

N2 - Background. Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus- independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. Methods. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. Results. There was an inverse relation between the patients' ages and the CD4+ T- lymphocyte counts six months after therapy was completed (r=-0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r=0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P=0.015). Conclusions. Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.

AB - Background. Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus- independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. Methods. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. Results. There was an inverse relation between the patients' ages and the CD4+ T- lymphocyte counts six months after therapy was completed (r=-0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r=0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P=0.015). Conclusions. Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.

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