Banding studies of chromosomal abnormalities in patients with acute lymphocytic leukemia.

Karyotypes were analyzed by routine Giemsa and quinacrine fluorescence for 16 patients with acute lymphocytic leukemia [ten adults (18 to 51 years) and six children (3 to 15 years)]. Four patients had received previous therapy, but all 16 had active disease when they were first studied. Eight patients (five untreated) had a normal karyotype initially; however, three of these developed a chromosomal abnormality during relapse. Eight patients had a chromosomal abnormality in their initial samples. Each of the 11 patients had different abnormalities. All chromosomes except Nos. 3, 5, 15, 16, and Y were involved in the various aneuploidies. One patient had a Ph1 chromosome due to a translocation with No. 21: t(21;22)(q22;q11). A patient with B-cell acute lymphocytic leukemia had a 14q+ marker in addition to other abnormalities. The median survival of patients with initially normal karyotypes may be longer than that of patients whose karyotypes are abnormal initially.

Granulopoietic effects of lithium on human bone marrow in vitro.

Although studies in mice suggest that lithium enhances granulopoiesis by increasing the production of colony stimulating factor (CSF), results using human assay systems have varied. We have studied the action of lithium on the in vitro proliferation of normal human bone marrow (BM) granulocytic progenitor cells (CFUc) and on CSF production by human peripheral blood (PB) mononuclear cells (MNC). In the absence of exogenous CSF, lithium increased the number of "spontaneous" BM CFUc (P less than 0.05). This effect was abolished by removal of phagocytic cells, suggesting that lithium does not affect CFUc directly, but rather acts via a phagocytic cell. Lithium variably increased BM CFUc when PB MNC feeder layers were employed as the CSF source. This stimulation was most pronounced when the number of cells in the feeder layer was low, i.e., suboptimal CSF. Incubation with 1 meq/L lithium, increased (P less than 0.05) CSF production by PB MNC. Addition of lithium to BM cultures containing optimum CSF did not increase, but in fact decreased, the number of CFUc. These studies indicate that lithium increases CSF production by both PB and BM MNC. Furthermore, the stimulatory effects of lithium occur when CSF levels in the culture system are low.

Sequential combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

Thirty-four patients with advanced squamous cell carcinoma of the head and neck have been treated with sequential combination chemotherapy consisting of Cytoxan, methotrexate, oncovin, bleomycin and adriamycin, followed by Leucovorin (COMBAL). All patients had undergone extensive prior radiation and/or surgery. All the patients had recurrent cancer. Toxicity included two deaths from drug induced pancytophenia and one from sepsis. Treatment was well tolerated and could be given in the outpatient clinic. No bleomycin pulmonary or adriamycin cardiac toxicity was seen. Results include 4 patients who achieved complete remission, objective improvement in measurable lesions in 6 others, stabilization of disease for 1 to 3 mo. in 5, and progression of disease in 13. Survival has ranged from 1 to 19+ months with a median of 10.7 mo. for patients that were evaluated. We conclude that COMBAL produces objective evidence of improvement in approximately 45% of patients with far advanced, previously treated squamous cell carcinoma of the head and neck.

Hodgkin's disease: problems of staging.

The preferred histopathological classification of Hodgkin's disease (HD) is that suggested by Lukes and Butler as modified at the Rye Symposium; the histologic subtypes are highly reproducible and correlate well with the anatomic sites of involvement, clinical stage, and survival. The accuracy of the bipedal lymphangiogram, 67gallium scan, and ultrasonography in predicting abdominal involvement by HD is 90% , 50%, and 88%, respectively. Staging laparotomy remains the most accurate method of detecting intra-abdominal disease and has added immensely to new concepts in the management of HD. These concepts suggest that patients with nodal disease limited to the celiac axis or upper para-aortic areas (substage III1) or pathologic stage (PS) IIIS+N-A, when treated with extended field radiotherapy alone have survival rates comparable to PS IIA patients. In contrast, patients in PS IIIA with lower abdominal nodal disease (substage III2), regardless of splenic involvement, have a prognosis comparable to PS IV disease. Thus, there may only be two stages of HD, those curable with extended mantle or smaller radiotherapy fields alone, and those requiring chemotherapy with or without supplemental radiotherapy.

Deletion of the long arm of chromosome 20 [del(20)(q11)] in myeloid disorders.

Detailed clinical and cytogenetic studies were performed in five patients who had abnormal hematopoiesis and an acquired deletion of an F-group chromosome. Cytogenetic analyses, with banding techniques, of cells from bone marrow, spleen, or unstimulated peripheral blood showed a partial deletion of the long arm of one chromosome 20 [del(20)(q11)] in all five patients. Three patients had myeloproliferative disorders of uncertain classification, the fourth had possible preleukemia, and the fifth had acute myelomonocytic leukemia. Although the five cases showed certain similarities, the clinical and hematologic findings seen with the 20q- abnormality were not specific. None of the patients showed evidence of polycythemia vera or idiopathic acquired refractory sideroblastic anemia, two diseases previously associated with the 20q-. Our studies indicate that the 20q- abnormality is not limited to diseases primarily affecting erythropoiesis but that it can be found in the broader spectrum of myeloid disorders. In polycythemia vera, the 20q- has sometimes been regarded as a possible result of previous therapy with cytotoxic agents; however, four of our patients were untreated when the deletion was first noted.

Lymphoblastic lymphoma in adults.

Clinical and cytogenetic studied were done on 12 patients with lymphoblastic lymphoma. The ages of the patients ranged from 17 to 58 years (median, 24.5 years). Males predominated by a ration of 5:1. Ten of the 12 patients had a mediastinal mass at diagnosis; two thirds of the patients had involvement of the bone marrow (3 of 12 patients initially were in a leukemic phase), and 5 of 12 patients had involvement of the central nervous system (CNS) with lymphoma. In all patients, the malignant cells were characterized by nuclear convolutions. Cytogenetic studies done on four patients showed clonal chromosome abnormalities in two cases. Six of the 12 patients were treated with the combination chemotherapy regimen COPA and received CNS prophylaxis; their survival was slightly longer than that of the other patients, who were treated with a variety of treatment regimens. Two of the 12 patients achieved a complete remission. The median survival of all patients was 11.5 months but was shorter in patients with initial CNS involvement or leukemia. The poor results achieved thus far in the treatment of this disease demand a new therapeutic approach.

Small-cell carcinoma of the lung: a five-year experience with combined modality therapy.

In the past five years, we have treated 89 patients with small-cell carcinoma of the lung with radiotherapy plus one of three chemotherapy programs. The 24 patients with disease confined to the chest (Stage IIIMO) had an 87% response rate to the combined modalities (79% complete responses) and a median survival of 18 months; 13 patients with disease confined to the chest and ipsilateral supraclavicular nodes (Stage IIIMOSCN +) had an 84% response rate (69% complete responses) and 11-month median survival; the 52 patients with distant metastases (Stage IIIMI) had a 71% response rate (15% complete responses) and eight-month median survival. Survival was not affected by adding prophylactic cranial irradiation to the latest regimen, although the CNS relapse rate was reduced. We conclude that our three chemotherapy programs to date differ very little in their effect on survival of patients with metastatic disease. New and more vigorous approaches, possibly including surgery, need to be tested for the management of disease confined to the chest. The designation of patients as Stage IIIMOSCN + is valid because such patients have better survival rates than patients with distant metastatic disease.