Coombs'-positive hemolytic anemia and ibuprofen.

A patient who developed an autoimmune hemolytic anemia during treatment with ibuprofen (Motrin) is described. Positive indirect Coombs' reaction was demonstrated with the patient's red blood cell eluate in the presence of the drug, supporting a drug-related immune hemolysis. The positive direct Coombs' reaction to anti-C3 antiserum strongly suggested that the immune hemolysis in this patient is probably mediated through complement alone; however, the presence of a small amount of IgG antibodies on the surface of the red blood cells which cannot be detected under conventional screening procedures cannot be completely excluded. Further studies, both clinical and laboratory, disclosed that the responsible ingredient in this particular instance appeared to be the orange dye coating of the Motrin-400 tablet rather than the ibuprofen itself.

Case report: familial thrombo-cytopenia in seven members of three generations.

All members in one generation and two of six members of the next generation were found to have familial thrombocytopenia. The disorder was transmitted as an autosomal dominant trait. Easy bruising and a bleeding tendency were the common features. No member had splenomegaly. Platelet counts varied from 8 to 75 x 10-9/liter, and there were no apparent morphologic abnormalities. Platelet survival studies using sodium chromate Cr 51-labeled autologous platelets were done for three members and showed shortened survival times. Two members were treated with corticosteroids and splenectomy without benefit. Three members tolerated surgery (splenectomy, polypectomy) without undue difficulty. Defective or ineffective thrombocytopoiesis appeared to be the basis of this hereditary disorder.

Adult acute leukemia: frequency of central system involvement in long term survivors.

The incidence and frequency of CNS relapses in long term surviving adults, age eighteen and over, covering the period 1967-1972, were presented. Four of 20 patients with ANLL and 12 of 24 patients with ALL were demonstrated to have CNS leukemia during the course of their illness. The onset of neurologic manifestation in three of four ANLL patients with CNS leukemia was observed within three months of the diagnosis, whereas it was delayed to 6-12 months interval in eight of 12 ALL patients. CNS relapses, a major determinant for CNS prophylactic and maintenance therapy, were observed in 75% of the patients with ALL and none in ANLL patients who were treated with I.T. chemotherapy and cranial radiation of 2000 R. Therefore, our observation suggests that CNS prophylactic and maintenance therapy should be of value in adults with ALL as in children; whereas, in ANLL, further observation is warranted before any definite therapy can be advocated.

Familial occurrence of colon and uterine carcinoma and of lymphoproliferative malignancies. II. Chromosomal and immunologic abnormalities.

Cytogenic and immunologic studies were performed on 20 members of a family who had an increased susceptibility to carcinomas of the colon, uterus and of lymphoproliferative malignancy. Chromosomal abnormalities such as small G and/or long submetacentric marker chromosome and other aberrations were observed in members who had cancer as well as some asymptomatic siblings. In addition, impairment of T cell function was noted in many of the members suggesting that defective cell-mediated immunity, which also may be genetically determined, played an important role in the expression of this disease.

Familial occurrence of colon and uterine carcinoma and of lymphoproliferative malignancies: clinical description.

Carcinoma of the colon occurred in four generations of a family, including two of three siblings of one generation and eight of 19 members of the next generation. In addition, uterine cancer or lymphoproliferative malignancies were found in two family members. Of 41 members of the fourth generation, two were found to have colon cancer and one had malignant lymphoma. Clinical features were similar to those patients with "cancer family syndrome." Although a precise genetic mechanism is uncertain, it appeared to be transmitted as an autosomal dominant character.

Second malignancies in patients with multiple myeloma.

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration approximately 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non=hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.

Adult central nervous system leukemia: incidence and clinicopathologic features.

Two hundred and seventy-two adults diagnosed between 1949 and 1971 as having acute leukemia were evaluated. Two hundred and fifty-seven patients had died and autopsies were obtained in 202 cases. Central nervous system (CNS) leukemia was demonstrated in 22 of 93 autopsies with acute nonlymphocytic leukemia (ANLL) during the period 1949 through 1966 and 8 of 47 during the period 1967 through 1971. Nine of 45 autopsies on acute lymphoblastic leukemia (ALL) patients diagnosed during 1949 through 1966 had CNS involvement, compared to 7 of 17 during 1967 through 1971. The median time from diagnosis of acute leukemia to CNS manifestations was two months for ANLL and six months for ALL. Headache, papilledema, and cranial nerve palsy were the common findings with meningeal leukemia. Early CNS involvement was observed in patients with high initial leukocyte/blast counts, low platelet counts, and early lymphadenopathy and hepatosplenomegaly. Ten of 13 patients treated between 1967 and 1971 with cranial irradiation and intrathecal chemotherapy responded; however, the duration of remission in ALL was short-lived with subsequent relapses at various intervals. In contrast, CNS recurrence in ANLL was rare. The value of CNS prophylactic and maintenance therapy is discussed.

Acute myelomonocytic leukemia associated with paraproteinemia.

A 49-year-old white woman with refractory anemia subsequently developed acute myelomonocytic leukemia with paraproteinemia 12 months later. The paraprotein was characterized as immunoglobulin G, type kappa, and the Bence Jones protein as free kappa chains. Further studies, including electron microscopy, cytochemistry, and immunofluorescence provided evidence for synthesis of the paraprotein, both in vivo and vitro, by the myelomonocytic leukemic cells.

Involvement of the central nervous system in non-Hodgkin's lymphoma.

Twenty-four patients with non-Hodgkin's lymphoma and CNS involvement are presented. There were 7 cases with diffuse histiocytic lymphoma (HL), 9 with diffuse poorly differentiated lymphocytic lymphoma (PDLL-D), of whom 6 patients were in leukemic conversion, 5 patients with nodular poorly differentiated lymphocytic lymphoma (PDLL-N), and 3 cases with undifferentiated lymphoma (UL). CNS complications were noted only in Stage IV lymphoma; the prognosis was generally poor. Histiocytic lymphoma was associated with widespread parenchymatous infiltration, whereas PDLL was usually associated with leptomeningeal seeding. The clinical course and the neuropathologic findings are discussed.