Arthur T. Skarin

Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival.

Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkins lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. We have reviewed ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981. All patients had biopsy-proven CNS lymphomas without systemic disease at presentation. In our series, control of CNS lymphoma was seen only in patients receiving craniospinal radiation or CNS-penetrating chemotherapy.

Improved survival following combined radiation therapy and chemotherapy for unfavorable prognosis stage I-II non-Hodgkin's lymphomas.

A retrospective analysis of 144 patients with stage I-II non-Hodgkins lymphoma (NHL) treated between June 1968 and December 1980 was performed. Patients were staged by bone marrow biopsy, chest radiography, blood chemistries, and either bipedal lymphangiography, computerized axial tomography, or surgical exploration of the abdomen. Patients were subclassified by extent of disease; minimal disease was defined as less than 10 cm and involved one or two contiguous sites, while patients with disease exceeding these limitations were considered to have extended stage I-II disease. Treatment consisted of radiation therapy (RT) alone in 74 patients and 70 patients were treated with chemotherapy with or without RT. Combination chemotherapy in patients with diffuse undifferentiated (DU) or diffuse histiocytic (DH) lymphoma resulted in a significantly higher 6-year survival as compared to patients treated with RT alone. For minimal disease DU/DH patients, the 6-year survival with chemotherapy +/- RT was 96% as compared to 61% with RT alone (P = .03). For extended disease DU/DH patients the 6-year survival with chemotherapy +/- RT was 56% as compared with 18% with RT alone (P = .003). This survival advantage from the initial use of chemotherapy was not seen in any of the other histologic subgroups.

Carcinoembryonic antigen: Clinical correlation with chemotherapy for metastatic gastrointestinal cancer

Serial carcinoembryonic antigen (CEA) titers were measured in 38 patients receiving chemotherapy for metastatic carcinoma of the colon, pancreas, and stomach. CEA levels were initially elevated (over 2.5 ng/ml) in 26 patients (12/20 colonic, 8/10 pancreatic, 6/8 gastric). Seventeen patients had rising serial CEA values during therapy; 13 had evidence of tumor progression, 3 had stable disease, and 1 had no measurable disease. Nineteen patients had stable CEA levels which were either persistently elevated (11 patients) or normal (8 patients). Ten of 11 patients with elevated CEA levels developed tumor progression. In 8 patients with consistently normal CEA levels, 6 (colon) had no evidence of progressive tumor, and 2 (1 pancreatic and 1 gastric) eventually died of metastatic disease. CEA levels decreased in 2 patients with colon carcinoma during remission from chemotherapy. A rising CEA titer often presages clinical deterioration, although elevated CEA levels may remain stable despite progressive disease. Persistently normal CEA, however, is a favorable prognostic sign. The limited effectiveness of chemotherapy for gastrointestinal cancer in this series precludes any definitive conclusion regarding the effect of chemother‐apeutically induced tumor regression on CEA levels, although there is suggestive evidence that CEA correlates with remission.

Combination chemotherapy of advanced lymphocytic lymphoma. Importance of histologic classification in evaluating response.

Thirty‐three patients with advanced lymphocytic lymphoma were treated with cyclophosphamide, vincristine, and prednisone (COP) administered in six weekly courses separated by 4‐week intervals for a total of six cycles. Thirteen patients (39%) achieved a complete remission (CR), and of these, 6 remain free of disease for 13–35 months. The median duration of CR is 19 months, compared to 5 months for partial responders (PR). Median survival for CR will exceed 31 months, compared to 10 months for PR and 2 months for nonresponders. Patients with nodular lymphocytic lymphoma (NL) had a significantly higher CR (77% or 10/13) and median survival (31 months) compared to those with diffuse lymphocytic lymphoma (DL) (12% CR or 2/17 with 7 months median survival). Eight of 13 patients (62%) with NL are alive for periods of 13–38 months. While more females had NL, the improved prognosis was related primarily to nodularity. COP as given in this study is useful in NL, but in DL alternate protocols are needed, especially in young adults who frequently develop superior vena cava syndrome, leukemia, and leukemic meningitis.

Muramidase in myeloproliferative disorders terminating in acute leukemia.

During serial studies of serum muramidase activity (SMA) over a 4‐year period on 168 patients with leukemia and myeloproliferative disorders (MPD) eight patients—one with polycythemia vera (PCV), one with agnogenic myeloid metaplasia, three with atypical myeloid metaplasia, and three with chronic myelogenous leukemia—developed acute myeloblastic or acute myelomonocytic leukemia (AMML). Onset of leukemia occurred early during the course of the disease and was associated with striking elevation of SMA in all six patients with AMML. Three patients studied in detail had significant hypokalemia possibly related to toxic effects of an excess of muramidase on renal tubules. Seven of the eight patients received therapy, consisting of splenic irradiation, alkylating agents, or both. Rapid rise of SMA in patients with MPD may herald the onset of acute leukemic metamorphosis.

Muramidase Activity in Leukemia and Myeloproliferative Disorders

Serum muramidase activity (SMA) was measured in 160 patients with leukemia and various myeloproliferative disorders (MPD). SMA was low in acute lymphocytic leukemia, variable in acute undifferentiated