Tin Han

An autopsy study of 1206 acute and chronic leukemias (1958 to 1982).

Autopsy data on 1,206 children and adult patients with acute myelocytic leukemia (AML) (585), chronic granulocytic leukemia (CGL) (204), acute lymphocytic leukemia (ALL) (308), and chronic lymphocytic leukemia (CLL) (109) obtained from 1958 to 1982 were reviewed. This analysis has shown that, whereas the proportion of patients with residual AML at any anatomic site decreased significantly and uniformly over the entire study period, significant corresponding decreases in patients with CGL and ALL occurred only since 1976 and 1978, respectively. No significant corresponding decreases were noted in patients with CLL at any time. Significant decreases were also noted over time in the rates of extramedullary site involvement by AML, CGL, and ALL. Whereas the lymphoreticular organs, kidneys, adrenals, and pituitary were most often involved at autopsy by CLL, the testes, leptomeninges, dura mater, uterus, large bowel, and pancreas were most often involved by ALL. In general, patients with AML and CGL showed the lowest relative rates of involvement of the various organs by leukemia during the 24‐year period. Whereas patients with AML and ALL showed significant decreases in the rates of involvement of nearly all anatomic sites during the most recent study periods, those with CGL and CLL showed corresponding decreases in only a few organ sites. The lower rates of organ involvement in patients with AML and ALL attest to the more aggressive eradication of leukemic cells by therapeutic regimens in these diseases over time. In particular, the significant decrease in the rate of meningeal involvement by ALL during the most recent period is probably attributable to central nervous system prophylaxis.

Immunologic impairment in bronchogenic carcinoma: A study of lymphocyte response to phytohemagglutinin

The in vitro lymphocyte response to phytohemagglutinin (PHA) was studied in 44 patients with bronchogenic carcinoma. The PHA responses of these patients varied greatly, with a mean which was significantly depressed as compared to that of normal individuals (p < 0.001). The lymphocyte response to PHA was markedly impaired in most patients with inoperable (late stage) disease, as compared to those with resectable tumors (p < 0.05). There may be a correlation between lymphocyte reactivity and survival with bronchogenic carcinoma.

Malignant lymphoma of pre-T-cell type terminating in acute myelocytic leukemia. A case report with enzymic and immunologic marker studies

We report a case of a T‐zone malignant lymphoma of a cervical lymph node developing in a 25‐year‐old man. Only 14% of the marrow was originally involved, but within two months massive, leukemic dissemination ensued. The blast cells were unable to bind sheep erythrocytes (E) but expressed human thymus leukemia antigen (HTLA) and common ALL‐stem‐cell (cALL) antigen and had high terminal deoxynucleotidyl transferase (TdT) and acid phosphatase activity. These findings suggest a malignant lymphoproliferative disorder of pre‐T‐cell type. Complete remission was achieved with intensive chemotherapy. Two months later, acute myelomonocytic leukemia was diagnosed; at this time, over 90% of the blast cells were peroxidase, sudan black, and chloracetate‐esterase positive. Consistent with loss of high TdT activity and HTLA and cALL antigens, 86% of the blasts now expressed Ia‐like antigens. Cytogenetic studies demonstrated hyperdiploidy. Reports of granulocytic leukemia in lymphoma are reviewed in the context of the above findings and the hypothesis that a leukemogenic factor affects a multipotential stem cell.

Chromosomes and causation of human cancer and leukemia. VII. The significance of the Ph1 in conditions other than CML.

Two cases of Ph1‐positive AML, and one case of Di Guglielmos syndrome are reported. A review of the literature reveals that the occurrence of a Ph1‐chromosome has been observed in a number of cases with these diseases, indicating that the Ph1‐chromosome is not solely specific for CML. By correlating cytogenetic and histologic bone marrow data, some evidence is presented that the process leading to the genesis of a Ph1‐chromosome may affect the bone marrow cells either at or beyond the stem cell level.

Indomethacin-mediated Enhancement of Lymphocyte Response to Mitogens in Healthy Subjects and Lung Cancer Patients

Indomethacin (prostaglandin synthetase inhibitor) was found to be capable of enhancing the mitogen‐induced lymphocyte proliferative responses of healthy subjects and patients with lung cancer. A whole‐blood culture technique was used. Indomethacin had no mitogenic activity. We observed a greater enhancement of lymphocyte response by indomethacin in weak responders as compared with strong responders in healthy subjects and lung cancer patients. A greater enhancement was also noted in lung cancer patients with active disease as compared with lung cancer patients in remission. In a separated cell culture system, the indomethacin exerted no effect on purified T cells in the absence of monocytes, while this agent exerted its enhancement effect on T lymphocyte response in the presence of autologous monocytes of lung cancer patients. This suggests that monocytes (suppressor cells) may secrete prostaglandins, which are responsible for the impairment of T lymphocyte response in lung cancer patients.

Treatment of early--stages I and II--nodular, poorly differentiated lymphocytic lymphoma.

Twenty-nine patients with Stages I and II nodular, poorly differentiated lymphocytic lymphoma were treated with radiation therapy or radiation therapy plus chemotherapy. Twenty-two patients with Stage I received radiation to the involved field, the other seven with Stage II received total lymphoid radiation. Complete remission was achieved in all 29. There were no differences in remission duration or survival according to treatment modality. Five of 29 (17%) patients relapsed. No relapses were observed after 5 years. Ten patients died; one patient died of lymphoma, and nine others died in continuous complete remission of various other causes. Sixty-six percent of the patients were alive at 74–160 months (median 118 months). Involved field radiation with or without chemotherapy was well tolerated, producing acceptable toxicity. Substantially more toxicity was observed after total lymphoid irradiation and although cures were also achieved, less toxic treatment programs should be investigated. The low rate of relapse observed in early stages of this lymphoma in this and in other studies is suggestive that cures might be achieved in nearly one-half of the patients presenting in early stage.

Clinical significance of cytogenetic findings in untreated patients with B-cell chronic lymphocytic leukemia

The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined. So-called polyclonal B-cell activators, i.e., pokeweed mitogen, Epstein-Barr virus, and lipopolysaccharide W from E. coli 055:B5, were used. Four out of 21 cases showed abnormal clones with trisomy 12 and were started on therapy shortly after the diagnosis and cytogenetic examination. On the other hand, most cases without abnormal clones had not received treatment for relatively long periods before and after cytogenetic examination. These findings may indicate that cytogenetic results can be utilized as a parameter for treatment and prognosis in B-CLL.

Cytogenetic evidence for clonal evolution in B-cell chronic lymphocytic leukemia

Sequential cytogenetic studies were performed in eight of ten patients with B-cell chronic lymphocytic leukemia presenting with trisomy 12 as the sole chromosomal abnormality. Follow-up studies of peripheral blood lymphocytes revealed that the karyotypes retained the sole abnormality of trisomy 12 in five cases, trisomy 12 converted to a normal karyotype during remission in one case, additional chromosome changes (-X,14q-) along with trisomy 12 appeared in one patient and multiple chromosome changes with or without trisomy 12 appeared in the remaining patient. The findings indicate that other chromosome changes in addition to trisomy 12 may develop as a result of clonal evolution or dedifferentiation, though the possibility that in two patients these changes may be related to chemotherapy and/or irradiation could not be ruled out entirely.

Sulfapyridine-Induced Serum-Sickness-Like Syndrome Associated with Plasmacytosis, Lymphocytosis and Multiclonal Gamma-Globulinopathy

W.B., a 38-year-old Negro, had previously been treated with sulfonamide ointment for dermatitis herpetiformis. On June 5, 1966, oral sulfapyridine, 2 gm daily, was started for a recurrence. Two wee...

Complete remission in chronic lymphocytic leukemia and leukolymphosarcoma

Seven instances of complete remission, confirmed by bone marrow aspiration, were observed among 202 patients with chronic lymphocytic leukemia and leukolymphosarcoma treated during a 10‐year period. Review of these cases and of 10 instances reported by others revealed that complete remission of disseminated lymphoproliferative disease was observed more frequently after x‐ray irradiation than after other modalities of treatment and that many remissions followed treatment which might be considered inadequate. The authors conclude that host factors must have played a major role in these cases but that in almost all of them improvement was clearly related to the administration of specific therapy. A characteristic pattern of response was associated with each therapeutic modality and x‐ray irradiation produced the most rapid correction of circulating lymphocytosis.