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predominant cell type occurring either spontaneously
or after therapy, while this appears to
be more unusual in de novo ALL or ANLL
(unpublished work).
111. Lympboproliferative Disorders
Recent studies by DonIon et al. (1977), Kung
et al. (1978), and ourselves (Mertelsmann et
al. 1978b, 1979a) have demonstrated the
clinieal significance of TdT determinations in
patients with non-Hodgkin's lymphoma (Table
1). In patients with lymphoblastic lymphomas
of the T and "null" cell type high levels ofTdT
were observed as seen in ALL. Because
a definitive histologie diagnosis is sometimes
diffieult to make in this group of patients we
have often found TdT determinations providing
important diagnostic information. Lymphoproliferative
diseases of the mature T and
B cell type have been found to be TdT( - )
(Table 1). Although diffuse histiocytic lymphomas,
whieh are diagnosed on the basis of
the presence of large cells resembling histiocytes,
generally represent B-cell proliferations,
a few cases of "true" histiocytie lymphomas
with cells exhibiting phagocytic properties
and more recently lymphomas of the null cell
type have been described which exhibited high
levels of TdT in involved tissue (Gordon et al.
1978; Mertelsmann et al. 1978b). Although it
is too early to determine the significance of
these marker studies for the response to
therapy and long-term prognosis in this group
of patients, all patients with lymphoid neoplasias
with high levels of TdT studied by us had
a characteristic clinieal course resembling that
of ALL.
IV. TdT Determinations in tbe Monitoring of
Disease Activity in TdT+ Neoplasia
We have reported significantly elevated TdT
levels in ALL bone marrow in complete
remission on and off therapy as compared to
normal controls (Mertelsmann et al. 1978b).
The TdT levels characteristically fluctuated,
whieh could not be explained by technical
problems or chemotherapy. A preliminary
analysis of our own data suggests an increased
risk of relapse in patients with persistently
elevated TdT values in eR. The clinical and
biologic signifieance of elevated Td)' levels in
ALL in patients in long-term remission off
chemotherapy remains to be analyzed; if
indicative of residual disease, this observation
would be important for the understanding of
the pathophysiology of leukemias and for the
design of therapeutic strategies.
E. Conclusion
From our own studies and work by published
others it appears that determination of TdT
activity and definition of cell phenotypes in
hematopoietie malignancies are useful tools
for the classifieation of these disorders and
have signifieant prognostic, c1inieal, and pathogenetie
implications. Although several
questions still remain unsolved, this comprehensive
approach, when correlated with c1inical
presentation and conventional morphology,
might help the physician by providing
objective diagnostic criteria for prognostic
subgroups unidentifiable by conventional methods.
Furthermore, this approach will help to
understand the underlying pathogenetic processes
leading to the clinieal syndromes of
human leukemias and lymphomas.
Acknowledgments
The skillful technical assistance of Ms. Loma Barnett
und Ms. Sa An Hu is greatly appreciated. We
would like to thank Ms. Cynthia Garcia for typing
the manuscript.
References
(Representative references were selected, which list
further literature regarding specific aspects of TdT.)
- Bollum FJ (1979) Terminal deoxynucIeotidyl
transferase as a hematopoietic cell marker. Blood
54: 1203-1215 - DonIon JA, Jaffe ES, Braylon Re
(1977) Terminal deoxynucIeotidyl transferase activity
in malignant lymphomas. N Engl J Med
297: 461-464 - Gordon SD, Hutton JJ, Smalley RV,
Meyer ML, Vogler WR (1978) Terminal deoxynucIeotidyl
transferase (TdT), cytochemistry, and
membrane receptors in adult acute leukemia. Blood
52:1079-1088 - Incefy GS, Mertelsmann R, Yata
K, Dardenne M, Bach JF, Good RA (1980) Induction
of differentiation in human marrow T -cell
percursors by the synthetic serum thymic factor,
FTS. Clin Exp Immunol 40:396-406 - Janossy G,
Bollum FJ, Bradstock KF, McMichael A, Rapson N,
Greaves MF (1979) Terminal transferase-positive
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