Thrombotic thrombocytopenic purpura: treatment with plasmapheresis.

Twenty-one episodes of thrombotic thrombocytopenic purpura (TTP) were treated with plasmapheresis. Adjunctive agents included corticosteroids, aspirin, dipyridamole, and vincristine. There were 17 patients; 12 were female. The median age was 41 years. Most patients presented with neurologic symptoms. Thrombocytopenia was profound with a mean initial platelet count of 14,900/mm3. The mean hematocrit on presentation was 26.7% and the mean LDH 1300 IU/L. Eighteen episodes responded completely following plasmapheresis/plasma exchange (86%). Response was prompt, the initial rise in platelet count occurred after a mean of four exchanges, and complete response (a platelet count over 150,000/mm3) was obtained after a mean of nine exchanges. Four of the episodes treated were relapses that occurred in three patients. All responders are alive with a median duration of follow-up of 20 months. The three patients who failed to respond have died. This report extends recent observations that the addition of plasmapheresis/plasma exchange to the therapy of TTP has significantly improved the outlook for patients with this disorder.

Comparison of in vitro and in vivo effects of vincristine and vindesine on leukemic cells from patients with chronic granulocytic leukemia in blast crisis.

We employed a liquid culture system to examine the in vitro effects of vincristine and vindesine on cellular incorporation of 35SO4 into leukemic cells obtained from 5 patients with chronic granulocytic leukemia in blast crisis. The per cent of 35SO4 into drug-treated as compared to saline-treated leukemic cells was compared to the clinical outcome of patients treated with these agents. A good or partial clinical response to vincristine or vindesine was seen in patients whose leukemic cells incorporated less than 50% 35SO4 when exposed to vincristine or vindesine in vitro, compared with control saline-treated cells. No clinical response was observed following treatment with vincristine or vindesine if the 35SO4 incorporation of drug treated leukemic cells was greater than 50% of saline-treated cells. These data suggest that the in vitro effects of vincristine or vindesine on 35SO4 incorporation into leukemic cells of patients in blast crisis may parallel the clinical outcome of patients treated with these agents in vivo.

Splenectomy for thrombocytopenia in chronic lymphocytic leukemia.

The role of peripheral platelet destruction as a reversible etiology of thrombocytopenia in chronic lymphocytic leukemia (CLL) was evaluated in nine patients with CLL and refractory thrombocytopenia who underwent splenectomy. The patients' ages ranged from 54 to 74 years. Progressive thrombocytopenia refractory to antineoplastic agents and corticosteroids had been present for a mean of 23.4 months. The platelet counts were 4,000-57,000/microliter, and were generally higher in those patients with larger spleens. The spleens ranged from 180 to 4050 gm. Seven patients responded completely to splenectomy, achieving platelet counts greater than 150,000/microliter, and in one other patient, the count rose to greater than 100,000/microliter. The platelet count of one patient failed to respond to surgery. Those patients with massive splenomegaly developed higher, more rapidly rising platelet counts postoperatively. No operative mortality was encountered. Median hospitalization was seven postoperative days. All patients experienced an increased sense of well-being. Median follow-up time is 9 months.

A rapid in vitro drug-sensitivity assay in acute nonlymphocytic leukemia.

Leukemic myeloid, myelomonocytic, and monocytic cells will incorporate radiolabeled sulfate into newly synthesized macromolecules. We developed a liquid culture technique to examine the in vitro effects of chemotherapeutic agents on the incorporation of radiolabeled sulfate into cells of patients with acute nonlymphocytic leukemia (ANLL). Cells recovered from bone marrow or peripheral blood of 25 patients with ANLL were incubated in vitro for one hour with saline (control) or a variety of chemotherapeutic agents. Cells were washed free of the drug and grown in liquid cultures containing nutrient medium and 35SO4. The percent of 35SO4 incorporated into the drug treated as compared with control cells was determined after one, three, and seven days of culture. Patients whose drug-treated cells incorporated less than 30% of 35SO4 when compared with the control after three or seven days of culture achieved a complete response to these agents in vivo (P less than .05). Thus, the in vitro effects of various chemotherapeutic agents on the incorporation of 35SO4 into cells obtained from patients with ANLL may help predict clinical response to these agents in vivo.

Acute nonlymphocytic leukemia complicated by severe cytophagocytosis of formed blood elements by nonmalignant histiocytes: cause of significant clinical morbidity.

A 52-year-old female presented with Philadelphia chromosome-positive acute nonlymphocytic leukemia and a morphologically benign-appearing histiocytosis with intramedullary cytophagocytosis of formed blood elements. No cause of the reactive histiocytosis could be found. Despite initial successful therapy of the acute nonlymphocytic leukemia with induction of a cytological remission, pancytopenia with marked cytophagocytosis persisted. Therapy aimed at reducing the degree of cytophagocytosis by the histiocytes, in the form of vinblastine-treated platelets and, subsequently, prednisone, was instituted. There was no significant clinical response to either therapeutic maneuver. Cytophagocytosis persisted until leukemic relapse and death ensued.