Patients Undergoing Induction Therapy Research Articles

The pathogenesis and clinical significance of cytologically detectable oral Candida in acute leukemia.

Using serial examination and oral cytology, 50 adult patients undergoing induction therapy for acute leukemia were studied for oral colonization with candida species. Ninety percent of patients were found to be colonized with Candida, with most of these colonizations present by day 14. The 30 patients exhibiting colonization with pseudohyphae received ketoconazole 400 mg daily by mouth. Of 20 patients in this group treated for 5 or more days, Candida organisms were eradicated in nine. Sixteen patients from the above group with persistent colonization on ketoconazole were treated by independent clinical decision for sustained fever and neutropenia with Amphotericin B, but only one responded by elimination of colonization. Seven of the 15 patients who did not initially receive ketoconazole developed Candida dissemination in contrast to two of 30 who received ketoconazole initially (P = 0.003, Fisher's exact test). No patient who initially had or acquired a negative cytology developed oral or disseminated candidiasis. Clinical oral candidiasis occurred in three patients, all of whom were receiving amphotericin B. Approximately 90% of these patients have or develop oral colonization with Candida organisms as identified by oral cytology. Those with colonization, both with and without pseudohyphae present, are at risk for dissemination. Amphotericin B does not eliminate colonization remaining after treatment with 400 mg of ketoconazole daily. More effective diagnostic and therapeutic strategies are needed to identify and eliminate Candida organisms and to prevent disseminated candidiasis in this population of patients.

Metabolism of fibrinogen in children with acute lymphoblastic leukaemia.

The metabolism and in vivo kinetics of fibrinogen were studied using homologous 125I-labelled fibrinogen in 21 children with acute lymphoblastic leukaemia (ALL). Ten patients were undergoing induction therapy, 11 children were in complete remission on maintenance therapy. Results in the patients undergoing induction therapy were: plasma fibrinogen levels were normal in all except one patient, the plasma fibrinogen pool was elevated in six cases, seven patients had a shortened fibrinogen half-life and increased fractional catabolic rate for fibrinogen. The absolute catabolic rate for fibrinogen was elevated in six cases. This shortened fibrinogen half-life together with the correcting effect of heparinisation on the fibrinogen turnover indicated that fibrinogen was consumed by chronic disseminated intravascular coagulation. Inhibition of the fibrinolytic system with epsilon-aminocaproic acid in five patients had no influence on the fibrinogen half-life in three of them but resulted in its prolongation in two patients. All except two children in complete remission had normal fibrinogen levels. Six patients had elevated plasma fibrinogen pools and in all of the cases survival and fractional catabolic rate of fibrinogen were normal. The absolute catabolic rate for fibrinogen was normal in eight, elevated in three of the patients. This observation indicates that fibrinogen synthesis remains accelerated in some cases of ALL in complete remission, but the cause of this is not known.

Combined granulocyte and platelet transfusions. Development of alloimmunization as reflected by decreasing cell recovery values.

Twenty-three patients undergoing induction therapy for acute myelogenous leukemia (AML) received a total of 191 combined prophylactic granulocyte (PMN) and platelet (PLT) concentrates on alternate days (median 8, range 3-12 per patient). Each transfusion was assessed by monitoring the patient for reactions and by estimating the recovery of PMN in the circulation at 1 hour and of PLT at 1 and 20 hours. Seventeen patients developed alloimmunization to PLT from at least one donor, defined as either a PLT recovery of less than 15 percent at 1 hour and/or less than 10 percent at 20 hours. In this group there was a progressive reduction in PMN and PLT recovery with increasing transfusion number, strongly suggesting alloimmunization to both cells. Thirty-four transfusions were accompanied by transfusion reactions, thirty-two of which occurred in ten patients who had PMN recoveries of less than 5 percent after at least one transfusion (median 2.5, range 1-6 transfusions per patient). Actuarial calculations predicted that 70 percent of patients would become alloimmunized to PLT from at least two individuals after receiving 11 transfusions. These results suggest that combined PMN and PLT transfusion are associated with the rapid development of alloimmunization.

Fibrinogen survival and fibrinolysis in acute leukemia

Fibrinogen survival using 125I-labelled homologous fibrinogen was studied in 17 adults with acute leukemia. Five patients in complete remission had normal fibrinogen survival and turnover rate. Five of 6 patients undergoing induction therapy and 4 of 6 in relapse had shortened fibrinogen survival; the turnover rate was increased in all 12 patients. Nine of 12 patients with active disease had elevated levels of fibrinogen degradation products in the serum. Serial coagulation studies did not support the diagnosis of overt disseminated intravascular coagulation. There was no correlation between the morphological type of leukemia, chemotherapy, the presence of fever and sepsis, or liver dysfunction and fibrinogen survival. Other possible causes of the accelerated fibrinogen turnover in patients with active disease are discussed.