John L. Ziegler

Acute tumor lysis syndrome: A review of 37 patients with Burkitt's lymphoma

Renal and metabolic complications of tumor lysis during 46 episodes of remission induction chemotherapy were reviewed in 37 patients with American Burkitts lymphoma. Azotemia occurred in 14 patients, preceding chemotherapy in eight. All of these patients had abdominal tumors. Pretreatment azotemia was associated with elevated lactic dehydrogenase (LDH) and uric acid levels, and sometimes extrinsic ureteral obstruction by tumor. Two patients required dialysis for uric acid nephropathy before chemotherapy was initiated. Following chemotherapy, major complications of tumor lysis (hyperuricemia, hyperkalemia and hyperphosphatemia) were associated with very large tumors, high LDH levels and inadequate urinary output. In patients undergoing diuresis and receiving allopurinol, hyperkalemia or hyperuricemia developed infrequently unless concomitant renal failure ensued. Hyperphosphatemia, which occurred only after chemotherapy, developed in 10 of 32 (31 per cent) nonazotemic and in all azotemic patients. Hemodialysis was required in three post-treatment patients for control of azotemia, hyperuricemia, hyperphosphatemia and/or hyperkalemia. Because of the potential for renal failure caused by precipitation of phosphate, severe hyperphosphatemia is an additional criterion for dialysis in patients with acute tumor lysis syndrome.

Treatment Results of 54 American Patients with Burkitt's Lymphoma Are Similar to the African Experience

Burkitts lymphoma in Africa may be curable by chemotherapy alone; in nonendemic regions results are reportedly less favorable. Fifty-four Americans with Burkitts lymphoma were treated with two sequential combined treatment regimens that incorporated therapeutic approaches from clinical trials in Africa. Four patients died during induction therapy, and 48 of the remaining 50 achieved complete remissions. Twenty-two relapsed at a median of three months from the start of therapy. The overall two-year actuarial survival was 54 percent: younger patients ( less than 12 years old) and patients with minimal tumor burden (stages A, B and AR) had significantly better survivals than older patients (P less than 0.02) and patients with advanced abdominal tumors (stages C and D) (P less than 0.01). No differences in survival were detected between patients treated at the National Institutes of Health and those treated in regional institutions on either protocol. Complete response rates, relapse frequency and survival in American patients are similar to results in Africa.

Non-Endemic Burkitt's Lymphoma: A B-Cell Tumor Related to Germinal Centers

To investigate the nature of non-endemic Burkitts lymphoma, we examined neoplastic cells from eight American patients for receptors for sheep erythrocytes (E), complement (EAC), and Fc fragment of lgG (igGEA), and for surface immunoglobulins (Slg) and hydrolytic enzymes. In addition, we reviewed 47 biopsies and 17 autopsies from American patients to ascertain patterns of involvement by tumor in lymph nodes, spleens and Peyers patches. Neoplastic cells in all cases studies bore monoclonal surface immunoglobulins of the igM class. Receptors for EAC and igGEA were identified on a minority of the cells. Little or no hydrolytic enzyme activity was demonstrable. These results indicate that, like Burkitts lymphoma in Africans, this histologically identical tumor in American patients consists of B lymphocytes. In 10 biopsies and two autopsies, germinal centers were selectively involved by tumor, suggesting that these neoplastic cells may be related to some B lymphocytes of normal germinal centers.

Kaposi's sarcoma in childhood: An analysis of 100 cases from Uganda and relationship to HIV infection

We report 100 cases of Kaposis sarcoma (KS) in children under 15 years of age treated at the Uganda Cancer Institute in the 6‐year period 1989–1994. The incidence of childhood KS has risen more than 40‐fold in the era of AIDS, and 78% of 63 cases tested were seropositive for HIV‐I. There were 63 boys and 37 girls. The median age was 4 years and the median age of onset was 33 months. Tumour distribution was lymphadenopathic and muco‐cutaneous, with 2 major patterns: pattern I, oro‐facial dominant (79%); and pattern II, inguinal‐genital dominant (13%). A newly described herpes‐like virus is implicated as the cause of KS (KSHV), and DNA sequences of this virus were present in all of 8 childhood cases tested. If KSHV is a direct cause of KS, this tumour distribution in children suggests mucosal routes of virus entry, possibly during birth or breast feeding. The dramatic increase of childhood KS implies that the prevalence of causative factors is rising in Uganda.

Pregnancy outcome following cancer chemotherapy

The outcome of pregnancies of patients who received aggressive chemotherapy was examined. Of 448 patients screened, 30 had 12 abortions (10 elective and two spontaneous) and 28 live births. Follow-up of off spring revealed no major malformations. In addition, growth, development and school performance were normal. These results support the contention that chemotherapy administered to women prior to gestation or after the first trimester may result in normal births in the majority of cases. Moreover, the available data suggest that chemotherapy given to men at or prior to the time of conception does not appear to result in fetal damage. These results may be of value in counseling cancer patients regarding risks to their offspring.

Prolonged complete remission following high dose chemotherapy of burkitt's lymphoma in relapse

Fourteen patients with American Burkitts lymphoma resistant to conventional chemotherapy were treated with high‐dose combination chemotherapy and intensive supportive care. Four patients died shortly after chemotherapy, 3 of an acute carditis. All ten remaining patients demonstrated tumor regression and 3 remain in prolonged complete unmaintained remission 29+, 19+, and 9+ months after treatment. These findings demonstrate that high‐dose chemotherapy will benefit some patients with Burkitts lymphoma unresponsive to conventional chemotherapy, but the medullary and extramedullary toxicity of this treatment strategy remains a formidable obstacle.

Immunological effects of BCG in malignant melanoma: two modes of administration compared.

Abstract A comparison was made of the effects of two modes of administering bacillus Calmette-Guerin (BCG) vaccine on the immunological reactivity of malignant melanoma patients after surgical exci...

Burkitt's tumor in the United States

Twenty American patients with tumors histologically and histochemically identical to African Burkitts tumor have been identified. These patients have been studied with regard to diagnostic criteria and clinicopathologic features of disease. In the 10 most recent patients, nontumor‐specific immune factors which might influence survival and responsiveness to standardized chemotherapy with cyclophosphamide have also been evaluated. Clinically, abdominal tumors dominate the clinical picture with jaw tumors second in frequency. Studies of immune factors revealed normal or only slightly deviated from normal immunologic capacity except for 3 patients who showed marked decrease in serum IgG. The tumor was found to be extremely sensitive to cyclophosphamide with high dose intermittent therapy providing the best results.

Cell kinetics in Burkitt lymphoma.

Abstract The cell kinetics of small pieces of diagnostic biopsies of African cases of Burkitt tumour was studied in 13 cases of primary tumour, 4 cases of recurring tumour and three cases of non-Burkitt lymphosarcomas in short time tissue culture with tritiated thymidine, ( 3 HTdr) in the medium. The in vivo uptake of 3 HTdr was also studied in two patients in Stage IV. The uptake of 3 HTdr by tumour cells in ascites fluid was studied in one patient. In 7 patients Colcemid was given 2–4 hr prior to a biopsy, and the number of Colcemid-arrested mitoses counted. In 4 cutaneous nodules of Burkitt tumour, the actual growth rate was measured. The results were analysed by means of a mathematical tumour growth model (see Appendix by R. Bjerknes). The kinetic parameters observed were as follows: actual clinical doubling time 66 hr, labelling index 17·34% , rate of cells entering DNA-synthesis 2·71% per hr, mitotic index 1·27% , rate of cells entering mitosis 1·75% per hr, duration of G 1 16·5 hr, duration of DNA-synthesis 6·5 hr, duration of G 2 2 hr, duration of mitosis 0·7 hr, potential doubling time based on labelling indices 25·6 hr, potential doubling time based on number of Colcemid arrested mitosis 39·6 hr, cell loss in the G 2 phase 30% , total cell loss factor 69% of maximum possible cell gain.

A phase II study of adriamycin (NSC 123127) in patients with hepatocellular carcinoma from Zambia and the United States

Nineteen Zambian and 22 American patients with hepatocellular carcinoma were treated with Adriamycin every three weeks in intravenous doses ranging from 20–75 mg/m2 (depending upon their initial serum bilirubin levels). Four of 16 (25%) „good risk”︁ Zambian and American patients who received 75 mg/m2 had objective responses, while in five additional patients there was evidence of either transient tumor regression or disease stabilization. In contrast three of 25 „poor risk”︁ patients who received 20–60 mg/m2 had objective responses. Even in this latter group, however, transient, objective signs of tumor regression were noted in four patients. The results of the present study confirm previous reports suggesting anti‐tumor activity for high doses of Adriamycin in hepatocellular carcinoma. Since those responses seen were generally incomplete and transient, further clinical trials of this agent used in combination or sequentially with other agents are indicated.