Anne I. Goldman

A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: clinical findings and clinicopathologic correlations in 15 patients.

Fifteen patients (11 males, four females; median age 57) manifested a disease characterized by (1) the histopathologic features of Castlemans disease, plasma cell type, in lymph node biopsies; (2) predominantly lymphadenopathic disease, involving multiple, preferentially peripheral nodal groups; (3) varied manifestations of multisystemic involvement (such as constitutional symptoms; splenomegaly and hypergammaglobulinemia; elevated ESR, anemia, and thrombocytopenia; hepatomegaly and altered liver function tests (LFTs); signs of renal disease); and (4) idiopathic nature. Two main patterns of evolution were recognized: persistent, with sustained clinical manifestations, and episodic, with recurrent exacerbations and remissions. Seventy-three percent of patients had infectious complications, and 27% developed malignancies. Complete remissions were obtained occasionally with antineoplastic agents and with splenectomy but not with glucocorticosteroids alone. The median survival time is 30 months; 60% of patients have died. Median follow-up in the six surviving patients is 97+ months. A review of 50 cases in the literature revealed similar clinical and laboratory features. Despite some similarities with autoimmune diseases, the main features of this process seem to best fit a hyperplastic-dysplastic lymphoid disorder in a setting of immunoregulatory deficit.

Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation.

In a randomized trial we studied the impact of providing total parenteral nutrition (TPN) to bone marrow transplant (BMT) patients during their cytoreductive therapy, and for 4 weeks following BMT, on 8 parameters of outcome. A total of 137 patients over 1 year of age and with normal nutritional status were randomized either to receive TPN starting one week prior to transplant or to receive hydration with a 5% dextrose solution containing electrolytes, minerals, trace elements, and vitamins. TPN was ultimately required by 40 of the 66 control patients when nutritional depletion was documented. Average total calorie and protein intake was significantly higher for the TPN group than for the control group. Minimum follow-up was 1 year and median was 2 years. Overall survival, time to relapse, and disease-free survival were significantly improved in the TPN group. Engraftment, duration of hospitalization, and incidences of acute and chronic graft-vs.-host disease and bacteremia were not different. Thus TPN during BMT had a positive effect on long-term outcome. Prophylactic nutritional therapy appears to be indicated even for well-nourished individuals during cytoreduction and BMT.

A Randomized Study of the Prevention of Acute Graft-versus-Host Disease

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 per cent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants.

A Comparative Trial of Didanosine or Zalcitabine after Treatment with Zidovudine in Patients with Human Immunodeficiency Virus Infection

BACKGROUND Both didanosine and zalcitabine are commonly used to treat patients with human immunodeficiency virus (HIV) infection who cannot tolerate zidovudine treatment or who have had disease progression despite it. The relative efficacy and safety of these second-line therapies are not well defined. METHODS In this multicenter, open-label trial we randomly assigned 467 patients who previously received zidovudine and had 300 or fewer CD4 cells per cubic millimeter or a diagnosis of the acquired immunodeficiency syndrome (AIDS) to treatment with either didanosine (500 mg per day) or zalcitabine (2.25 mg per day). RESULTS After a median follow-up of 16 months, disease progression or death occurred in 157 of 230 patients assigned to didanosine and 152 of 237 patients assigned to zalcitabine, for a relative risk of 0.93 for the zalcitabine group as compared with the didanosine group (P = 0.56), which decreased to 0.84 (P = 0.15) after adjustment for the CD4 count, Karnofsky score, and presence of AIDS at base line. There were 100 deaths in the didanosine group and 88 in the zalcitabine group, for a relative risk of 0.78 (P = 0.09) and an adjusted relative risk of 0.63 (P = 0.003). A majority of patients in each group (66 percent) had at least one adverse event during treatment (153 patients taking didanosine and 157 taking zalcitabine). Peripheral neuropathy and stomatitis occurred more often with zalcitabine and diarrhea and abdominal pain more frequently with didanosine. CONCLUSIONS For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death.

Six-year follow-up of the clinical significance of karyotype in acute lymphoblastic leukemia

To evaluate the importance of pretreatment karyotype in predicting long-term outcome in acute lymphoblastic leukemia (ALL), we performed a follow-up study of the 329 patients from the Third International Workshop on Chromosomes in Leukemia. Living patients have now been followed a minimum of 6 years. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, rearrangements involving 8q24, t(4;11), 14q+, 6q-] or, in the remaining cases, modal number (less than 46, 46, 47-50, greater than 50). As previously reported for achievement and duration of complete remission, and overall survival, disease-free survival differed significantly (p less than 0.001) among chromosome groups for both adults and children. Among children, karyotype was an independent prognostic factor for predicting disease-free survival. Because of the long follow-up, we now have been able to utilize statistical models to estimate the percentage of patients cured, according to karyotype alone and combined with other risk factors. Adults with the highest likelihood of cure (21-33%) were those patients with FAB-L1, a leukocyte count of 50,000/microliters or less, and one of the following chromosome groups: greater than 50, 47-50, 6q-, or normal. In children these same characteristics were associated with the highest percentage of cure (58-71% cured). In addition, we identified several groups of children with less than 15% chance of cure who clearly need to be treated as high-risk patients at diagnosis. Future studies of patients who have received risk-adapted therapy based on these chromosome data are needed to determine if more intensive treatment will improve the outlook of patients with cytogenetically unfavorable types of ALL.

Clinical Significance of Chromosomal Abnormalities in Acute Nonlymphoblastic Leukemia

Summary Seven hundred sixteen newly diagnosed patients were studied, to determine the clinical significance of chromosome analysis in ANLL. Karyotypes were classified in two ways. Cases were grouped into three categories, based on the presence of normal and abnormal metaphases. Cases were grouped into 12 categories based on more specific chromosome abnormalities (modified Chicago Classification). Both methods of classifying karyotypes, but especially the Chicago Classification, resulted in groups of patients with de novo ANLL with significantly different presenting clinical and hematologic features, including FAB type, leukocyte count, percent peripheral myeloblasts, platelet count, and DIC. Among patients with de novo ANLL, karyotypes, when classified according to the Chicago Classification, significantly correlated with frequency of initial complete remission and survival; the presence of normal and abnormal metaphases correlated with duration of first remission and survival. Among 305 intensively treated patients, the Chicago Classification also correlated with duration of first remission. Although both ways of classifying karyotype correlated with survival, even when other major risk factors in ANLL were considered, only the Chicago Classification was an independent prognostic factor among the intensively treated patients.

Prognostic significance of mediastinal involvement in Hodgkin's disease treated with curative radiotherapy

We evaluated the prognostic significance of mediastinal involvement in Hodgkins disease in 79 consecutive newly diagnosed patients treated with curative‐intent, nodal radiotherapy. Mediastinal masses were classified large or small depending on whether the ratio of the largest transverse diameter of the mass to the transverse diameter of the thorax at T5–6 was >.35. Forty‐eight patients had mediastinal disease; 20 had large masses, and 28 small masses. Complete remissions were achieved in 19 patients with large masses, 26 with small masses and all patients with no mediastinal masses. Relapses have occurred in 74% of patients with large masses but in only 27% with small masses and 19% without masses (P < .001). This high recurrence rate among patients with large masses could not be explained by other known adverse prognostic factors. Survival was adversely influenced by mediastinal mass size (P = .03). We conclude that curative‐intent, nodal irradiation is inadequate therapy for patients with large mediastinal masses. Controlled studies are needed to determine if survival can be improved by the addition of chemotherapy or whole lung irradiation.

IMPACT OF DELAY IN DIAGNOSIS ON CLINICAL STAGE OF TESTICULAR CANCER

Abstract Of 335 patients with germ-cell testicular cancer, 87·5% of the patients had symptoms related to the testis. Only 40% of the patients saw a physician within 2 weeks. Similarly, testicular signs were present in more than 90% of patients, but in only 61% of patients was a correct diagnosis made within 2 weeks of the initial physician visit. The length of the patient-related and physician-related delay was directly related to the clinical stage of the cancer at diagnosis. The median patient-plus-physician delay for stage I was 75 days, for stage II, 101 days, and for stage III, 134 days (p=0·017). Education programmes for the public and for physicians are needed to reduce delay in diagnosing testicular cancer.

Group counseling in adult patients with advanced cancer

The effect of a structured, interdisciplinary group counseling program was studied in 30 newly diagnosed adult patients with advanced cancer. These were compared to 30 patients who did not undergo group counseling. Group counseling resulted in a significant improvement in patient perception and self‐concept. This structured educational and psychological support program provided a mutual support experience for newly diagnosed patients with advanced cancer. Cancer 43:760–766, 1979.

Clinical Utility of Lymphocyte Surface Markers Combined with the Lukes-Collins Histologic Classification in Adult Lymphoma

To determine whether analysis of lymphocyte surface markers adds clinically useful information to the Lukes-Collins classification of lymphomas, tumors from 107 adults were histologically classified and studied for surface markers. Ninety-six cases were histologically classified as Lukes-Collins B-cell lymphomas; 87 showed B and one showed T surface markers, whereas eight had neither marker. Eleven lymphomas were histologically T-cell tumors; four of the 11 showed T surface markers, and seven had neither marker. Both the Lukes-Collins classification and surface markers identified patient groups with different clinical characteristics, chemotherapeutic responsiveness and survival. However, by combining surface markers and histologic features, additional important therapeutic and prognostic information was obtained. In each histologic class, patients whose lymphomas failed to express immunologically the histologically predicted marker had fewer responses to chemotherapy and shorter survivals than patients whose lymphomas expressed the predicted marker. Our data suggest that the analysis of surface markers in combination with the Lukes-Collins classification identifies many patients who respond poorly to current therapy and who thus require new therapeutic approaches.