Patients Undergoing Remission Induction Chemotherapy Research Articles

Redefining Remission Induction Chemotherapy Ineligibility by Early Mortality in De Novo Acute Myeloid Leukemia.

The therapeutic strategies for acute myeloid leukemia (AML) patients ineligible for remission induction chemotherapy have been improving in the past decade. Therefore, it is important to define ineligibility for remission induction chemotherapy. We retrospectively assessed 153 consecutive adult de novo AML patients undergoing remission induction chemotherapy and defined early mortality as death within the first 60 days of treatment. The 153 patients were stratified into the early mortality group (n = 29) and the non-early mortality group (n = 124). We identified potential factors to which early mortality could be attributed, investigated the cumulative incidence of early mortality for each aspect, and quantified the elements. The early mortality rate in our study cohort was 19.0%. Age ≥ 65 years (odds ratio (OR): 3.15; 95% confidence interval (CI): 1.05–9.44; p = 0.041), Eastern Cooperative Oncology Group performance status ≥ 2 (OR: 4.87; 95% CI: 1.77–13.41; p = 0.002), and lactate dehydrogenase ≥ 1000 IU/L (OR: 4.20; 95% CI: 1.57–11.23; p = 0.004) were the risk factors that substantially increased early mortality in AML patients. Patients with two risk factors had a significantly higher early mortality rate than those with one risk factor (68.8% vs. 20.0%; p < 0.001) or no risk factors (68.8% vs. 9.2%; p < 0.001). In conclusion, older age, poor clinical performance, and a high tumor burden were risks for early mortality in AML patients receiving remission induction chemotherapy. Patients harboring at least two of these three factors should be more carefully assessed for remission induction chemotherapy.

Posaconazole for the prophylaxis of invasive aspergillosis in acute myeloid leukemia: Is it still useful outside the clinical trial setting?

Background:Posaconazole prophylaxis during remission induction chemotherapy not only decreases the incidence of invasive aspergillosis (IA) but also improves the overall survival rate among patients with acute myeloid leukemia (AML). However, it remains debatable whether this result applies to patients in a real-world setting.Methods:We retrospectively assessed 208 adult patients with newly diagnosed AML who underwent remission induction therapy. These 208 patients were stratified into the posaconazole prophylaxis group (n = 58) and no antifungal prophylaxis group (n = 150).Results:Multivariate analyses showed that induction failure significantly increased the risk of proven or probable IA during the first induction chemotherapy [hazard ratio (HR), 10.47; 95% confidence interval (CI), 1.73–63.45; p = 0.011] and the entire course of AML treatment (HR, 4.48; 95% CI, 1.71–11.75; p = 0.002). However, posaconazole prophylaxis did not reduce the risk of IA during the first induction chemotherapy (HR, 1.47; 95% CI, 0.14–15.04; p = 0.746) and during the entire course of AML treatment (HR, 1.09; 95% CI, 0.29–4.09; p = 0.896). Furthermore, there was no significant difference in overall survival between these two groups of patients (514 versus 689 days; p = 0.454).Conclusion:Successful induction remains fundamental to reducing the risk of IA among AML patients undergoing remission induction chemotherapy.

328P - Acute kidney injury in newly diagnosed acute myeloid leukemia patients undergoing remission induction chemotherapy: Experience of a tertiary cancer centre of India

328P - Acute kidney injury in newly diagnosed acute myeloid leukemia patients undergoing remission induction chemotherapy: Experience of a tertiary cancer centre of India

Comparison of Plasma Concentrations of Posaconazole with the Oral Suspension and Tablet in Korean Patients with Hematologic Malignancies.

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.

Impact of Red Blood Cell and Platelet Transfusions in Acute Myeloid Leukemia (AML) Patients Undergoing Remission Induction Chemotherapy

Background: Induction chemotherapy (IC) in Acute Myeloid Leukemia (AML) leads to significant bone marrow suppression. The standard clinical practice to prevent or manage cytopenia related complications, namely anemia or bleeding, has been red blood cell (RBC) and platelet (PLT) transfusion. Accumulating evidence suggests no advantage to patients (pts) managed with liberal transfusion strategies compared to a restrictive approach. However, prior studies excluded patients with bone marrow failure conditions such as AML; hence it remains unclear whether a similar approach can be extrapolated for AML pts. We undertook this study to evaluate the effects of transfusions on treatment outcomes and complications in AML.Methods: Adult pts diagnosed with AML (excluding acute promyelocytic leukemia) at the Cleveland Clinic from 01/2008 - 12/2012 who underwent IC with 7+3 (full dose of cytarabine and anthracycline) and had complete adverse event data were included. Variables including demographics, preexisting comorbidities, AML disease characteristics, organ dysfunction (neurologic, cardiac, pulmonary, renal, hepatic, bleeding and thromboembolic events), infections (bloodstream infection, pneumonia and clostridium difficile associated diarrhea) and treatment response [complete remission (CR), incomplete remission (CRi), persistent disease (PD) and 30-day mortality] were assessed. The outcome of interest was any correlation between the total number of PLT and/or RBC transfusions and (i) organ impairment, (ii) infections, and (iii) treatment outcomes during the induction period. Culture confirmed bloodstream infections included vancomycin resistant enterococcus (VRE), gram-positive bacteria (except VRE), gram-negative bacilli and fungemia. Univariable and multivariable logistic regression models adjusted for potential confounders were performed for each outcome category. Odds ratio (OR) with 95% confidence intervals (CI) are reported.Results: Of 192 pts, 48% (n=93) were female, 85% (n=163) were Caucasian, 54% (n=103) were <60 years, (yrs, range, 19-82), and 17% (n=33) received 2 cycles of induction chemotherapy. Disease characteristics were - de novo AML 89% (n=170) and secondary AML 12% (n=22). Cytogenetic risk groups per CALGB 8461 criteria were - favorable 21% (n=41), intermediate 46% (n=89), unfavorable 24% (n=46), and unknown cytogenetics 8% (n=16). 67% of patients achieved CR (n=128), 15% (n=29) achieved CRi and 14% (n=27) had PD following IC. The median number of RBC and PLT transfusions received during remission induction chemotherapy was 12 RBCs (range 0-49) and 10 PLTs (range 0-62) (figure 1 and 2).In univariable analysis a higher number of RBC and PLT transfusions was associated with an increased risk of bloodstream infections (OR=1.03; CI,1.01-1.05; p=0.001). In multivariable analysis increased number of transfused RBCs and PLTs was associated with lower CR rates (OR=0.94; CI,0.91-0.97; p<0.001) and slightly increased risk for major adverse cardiac events (OR=1.04; CI,1.02-1.07; p=0.002), pulmonary events (OR=1.04; CI,1.02-14.07; p=0.004), neurologic events (OR 1.14; CI,1.07-1.22; p<0.001) and VRE bacteremia (OR=1.04; CI,1.01-1.08; p=0.005). There was no statistically significant association between transfusion and renal dysfunction (OR 1.02; CI,0.99-1.06, p=0.15), liver injury (OR=1.02; CI,1.00-1.05; p=0.067), thromboembolic events (OR=1.02; CI,0.98-1.05; p=0.28), total number of blood stream infections (OR 1.03; CI,1.00-1.05; p=0.019) and 30-day mortality (OR=0.98; CI,0.93-1.03; p=0.56).Conclusion: In multivariable analysis the number of RBC and PLT transfusions during AML IC is associated with a slightly increased risk for cardiac, pulmonary and some infectious complications. Higher numbers of transfusions also appear to be associated with lower CR rates. These data can inform future prospective studies designed to determine the benefits and risks of a restrictive transfusion policy in the AML population. [Display omitted] [Display omitted] DisclosuresSekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on Posaconazole Prophylaxis.

Posaconazole is a new oral triazole with broad-spectrum antifungal activity. Posaconazole has also shown a significant advantage of preventing invasive fungal infection compared to fluconazole or itraconazole in patients with prolonged neutropenia. Indeed, posaconazole has been commonly used for antifungal prophylaxis in patients undergoing remission induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. We experienced a case of fatal mucormycosis despite posaconazole prophylaxis. To our knowledge, this is the first reported case of fatal breakthrough mucormycosis in a patient receiving posaconazole prophylaxis during remission induction chemotherapy in Korea. This case demonstrated that breakthrough fungal infection can occurs in patients receiving posaconazole prophylaxis because of its limited activity against some mucorales.

Effect of Early Non-Hematologic Treatment Toxicity on Complete Remission (CR) and Time to CR in Acute Myeloid Leukemia Patients Undergoing Remission Induction Chemotherapy

Background: Acute Myeloid Leukemia (AML) patients (pts) being screened for clinical trials are often excluded based on laboratory values outside the normal range because of concerns of early treatment-related toxicities that can lead to adverse outcomes including death or delayed time to complete remission (CR). It has been shown that the time to achieve CR (Tc) has greater prognostic value in predicting survival than achieving CR per se (Estey et al., Blood 2002). In this study we assessed correlations between pretreatment risk factors and early (within 30 days of induction) treatment-related non-hematologic toxicities (TNHT) following IC, and between these toxicities and Tc and the probability of achieving CR.Methods: Adult pts diagnosed with AML (excluding acute promyelocytic leukemia) at the Cleveland Clinic from 10/08 - 11/12 who underwent IC with 7+3 (cytarabine and anthracycline) and had complete toxicity data were included. Variables including demographics, AML disease characteristics, abnormal laboratory measurements at diagnosis and during treatment, treatment response, and ICU stay, were assessed. The outcome of interest were development of non-fatal early TNHT and its effect on CR and Tc. TNHT were mapped as linear distance beyond the normal laboratory range and were set to zero if within limits. This was done for serum sodium (Na), potassium (K), bicarbonate, liver enzymes (AST, ALT), total bilirubin, INR (international normalized ratio), serum creatinine and albumin. These metrics were analyzed as a function of covariates at diagnosis using standard linear regression. They were then treated as covariates in logistic regression models of CR and in linear models of Tc. Akaike’s Information Criterion (AIC) was used in stepwise logistic regression model selection. Due to multiple testing, parameters are reported as significant only if p<0.01.Results: Of 91 pts, 58% (n=53) were female, 80% (n=73) were Caucasian, 64% (n=58) were younger than 60 years, the median age at treatment was 53.4 years (range 22.2 to 77.2), 13.2% (n=12) received 2 cycles of induction therapy and 30% of pts (n=27) required ICU care. Disease characteristics (per WHO classification) were – AML with recurrent cytogenetic abnormalities 31% (n=28), secondary AML 27% (n=24), therapy-related AML 6% (n=5), AML not otherwise specified 34% (n=31), myeloid sarcoma 1% (n=1) and unknown 1% (n=1). Cytogenetic risk groups per CALGB 8461 were – favorable 15% (n=14), intermediate 54% (n=49), unfavorable 23% (n=21), monosomal karyotype 7% (n=12) and unknown cytogenetics (n=7). BMI groups at diagnosis included normal (18.5-24.9, 28%), overweight (25-29.9, 29%), moderately obese (30-39.9, 29%), severely obese (>40, 12%) and one was underweight. All patients developed TNHT following IC: 98% (n=89) had electrolyte abnormalities, 26% (n=24) had elevated serum creatinine levels and 99% (n=89) had abnormal liver function indicated by AST, ALT, bilirubin, albumin and INR. Overall, 68% pts achieved CR, 9% (n=8) had complete response with incomplete recovery of counts, 10% (n=9) had persistent disease and in 12, determination of CR was not done due to early death or severe debilitation. Of all pretreatment variables, advancing age correlated with worsening hypoalbuminemia (p=0.0076); higher WBC with worsening hyperkalemia (p=0.001); absolute neutrophil counts with high K (p=.0002); and LDH with high K levels (p<< 0.0001) and elevations in ALT (p=0.0004) and AST (p=0.0002). Among early TNHT, worsening hyperkalemia (p=0.004) and acidemia (low bicarbonate levels) (p=0.008) correlated with less likelihood of achieving CR. In a multivariate analysis using stepwise logistic regression and AICs, none of the covariates in the final model for CR retained significant P values. None of the covariates independently predicted for Tc in the best fitted stepwise regression linear model.Conclusion: In pts considered fit to undergo 7+3 IC with potential curative intent, none of the baseline pretreatment variables independently predicted for early TNHT and occurrence of TNHT did not affect the probability of CR or Tc. Our data suggest that decisions regarding clinical trial eligibility or intensive therapy should be based on predicted risk of early treatment-related death rather than arbitrary age cut-offs and or abnormal laboratory values. DisclosuresSekeres:Celgene: Membership on an entity’s Board of Directors or advisory committees; Amgen Corp: Membership on an entity’s Board of Directors or advisory committees; Boehringer-Ingelheim Corp: Membership on an entity’s Board of Directors or advisory committees. Mukherjee:GlaxoSmithKline: Research Funding.

Time to Complete Remission As a Function of Kinetics of White Blood Cell Elimination and Recovery in Acute Myeloid Leukemia Patients Undergoing Remission Induction Chemotherapy

Background: While achieving complete remission (CR) is a major treatment milestone in acute myeloid leukemia (AML) patients (pts) undergoing induction chemotherapy (IC), it is the time to achieve CR (Tc) that has greater prognostic value in predicting subsequent survival. We are particularly interested in seeing whether trends in white blood cell (WBC) count elimination and recovery during induction phase can aid in prediction of Tc, thus enabling real-time prognostication.Methods: Adult pts diagnosed with AML (excluding acute promyelocytic leukemia) at the Cleveland Clinic from 10/08 - 11/12 who underwent IC with 7+3 (cytarabine and anthracycline) and achieved CR were included. Pretreatment variables including age, gender, race, smoking status, body mass index at dx, peripheral blood counts at diagnosis (dx), peripheral and marrow blasts at dx, disease classification and metaphase cytogenetics (per CALGB/Alliance 8461 criteria) were assessed. For mapping WBC elimination and recovery kinetics, we collected data on total WBC, absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) at several different time points after IC – day 1, day 7, day 14 (range, 13-17), day 21, day 35 (range 30-45) and the day CR was achieved. Time intervals selected for analysis included time taken for clearance of peripheral circulating blasts; time to reach nadirs for WBC, ANC and ALC; and time to ANC recovery (from ANC nadir to > 500/µL). Tc was assessed as a function of WBC, ANC and ALC measurements (at the above predefined time points); time intervals; and magnitude of drop and rise in WBC, ANC and ALC (log reductions and improvements in counts) using multivariable logistic and Cox proportional hazards models and stepwise regression using Akaike’s Information Criterion (AIC) for model selection. Due to multiple testing, parameters are reported as significant if p<0.01. Cell counts and time interval metrics were also analyzed as a function of pretreatment covariates using standard linear regression.Results: Of 80 pts, 58% (n=46) were female, 79% (n=63) were Caucasian, 68% (n=54) were younger than 60 years, the median age at treatment was 53.5 years (range, 19 to 77) & 18% (n=14) received 2 cycles of induction therapy. Twenty one pts (26%) had secondary AML. Disease characteristics (per WHO classification) were – AML with recurrent cytogenetic abnormalities 31% (n=25), secondary AML 27% (n=22), therapy-related AML 6% (n=5), AML not otherwise specified 34% (n=26), myeloid sarcoma 1% (n=1) and unknown 1% (n=1). Cytogenetic risk groups per CALGB 8461 were – favorable 19% (n=15), intermediate 53% (n=42), unfavorable 23% (n=18), & unknown cytogenetics (n=5). In the final model of a multivariable stepwise regression analysis, none of the cell counts at the defined time points of IC predicted for Tc. Of pretreatment covariates, only male sex correlated slightly with longer Tc (p=.04). Longer times to reach ANC (p=.01) and ALC (p=.03) nadirs had borderline correlations with longer Tc. In contrast, longer times to reach ANC > 500/µL was significantly associated with delayed Tc (p<<.001). Greater fold change drop and rise in ANC counts correlated with Tc but was not significant at the p<.01 level.Conclusions: In this study the only WBC cell kinetic parameter post IC that independently predicted Tc was time to ANC recovery, which seems intuitive. Biologically, this could represent resiliency of the underlying hematopoietic stem cell reserve which is a function of age, prior therapies or antecedent hematologic disorder. Interestingly, in our series, WBC kinetics did not correlate with the number of induction cycles required (1 vs. 2), age (using age cut-offs of 60 and 70 years) or body mass index. Although the concept of using WBC kinetics during IC as a clinical surrogate for chemotherapy responsiveness or toxicity (overdosing vs. underdosing) is appealing, it is not supported by our data. DisclosuresSekeres:Celgene: Membership on an entity’s Board of Directors or advisory committees; Amgen Corp: Membership on an entity’s Board of Directors or advisory committees; Boehringer-Ingelheim Corp: Membership on an entity’s Board of Directors or advisory committees. Mukherjee:GlaxoSmithKline: Research Funding.

Treatment cost development of patients undergoing remission induction chemotherapy: a pharmacoeconomic analysis before and after introduction of posaconazole prophylaxis

Prior clinical trials have demonstrated efficacy and effectiveness of posaconazole in the prophylaxis of invasive fungal diseases in high-risk patients. Controversy exists about the cost-effectiveness of this approach. We performed an analysis comparing the direct costs of posaconazole prophylaxis against polyene mouthwash (thrush) prophylaxis in patients with acute myelogenous leukaemia (AML). Data of AML patients receiving remission-induction chemotherapy were extracted from the CoCoNut (Cologne Cohort of Neutropenic Patients) database to compare hospital costs of patients before (2003-2005) and after (2006-2008) introduction of posaconazole prophylaxis. Treatment on general ward, intensive care unit (ICU), mechanical ventilation, diagnostic procedures, and all anti-infectives were calculated. Patient groups were well matched according to age, gender and duration of neutropenia. The mean costs per patient in the posaconazole group (n=76) and the polyene mouthwash group (n=81) were €21040 (95% confidence interval (CI): €18204-€23876) and €23169 (95% CI: €19402-€26937) per patient. Antifungal treatment costs were €4580 (95% CI: €3678-€5482) and €4019 (95% CI: €2825-€5214). Duration on the ICU was 2582 (95% CI: 984.1-4181.7) and 5517 (95% CI: 2206-8827.3) min. In our hospital, primary antifungal prophylaxis by posaconazole was cost-effective. There was a trend towards cost savings, which was primarily caused by a shorter overall length of stay and the less frequent ICU treatment.

PIN34 Development of Treatment Costs of Patients Undergoing Remission Induction Chemotherapy: A Historical Comparison Before and After Introduction of Posaconazole Prophylaxis

PIN34 Development of Treatment Costs of Patients Undergoing Remission Induction Chemotherapy: A Historical Comparison Before and After Introduction of Posaconazole Prophylaxis

High incidence of bloodstream infection detected by surveillance blood cultures in hematology patients on corticosteroid therapy

The aim of our study was to evaluate the frequency of "occult" bacteremia/fungemia as well as the diversity of pathogens involved in hematology patients treated with corticosteroids. Daily surveillance blood cultures were taken from patients treated with corticosteroids as part of their intensive chemotherapy or during graft-versus-host disease following hematopoietic stem cell transplantation during a 3-year period (2006-2009). We reviewed the frequency of occult bacteremia/fungemia as well as the pathogens involved. During the 3-year period, 3,821 bottles were cultured from 215 patients and 4.9 % of the bottles tested were positive. Surveillance blood cultures revealed bloodstream infection in 24 % of the patients (definite bloodstream infection in 16 %). Seventy-five percent of patients were still afebrile when microorganisms were detected. The main risk group was acute lymphocytic leukemia patients undergoing remission induction chemotherapy. The pathogens cultured most frequently were coagulase-negative staphylococci, enterococci, Escherichia coli, and Pseudomonas aeruginosa. A high incidence of occult bacteremia was detected by surveillance blood cultures. Further studies are needed to evaluate if a strategy based on surveillance blood cultures can reduce mortality related to bloodstream infections.

A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML)

Invasive fungal infections remain a frequent cause of morbidity and mortality in long-term neutropenic patients. The availability of tolerable broad-spectrum antifungals like voriconazole stimulated the discussion about optimal timing of antifungal therapy. We conducted a trial to analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for acute myelogenous leukaemia (AML). This was a prospective, randomised, double-blind, placebo-controlled phase III trial in AML patients undergoing remission induction chemotherapy. Oral voriconazole 200 mg twice daily or placebo was administered until detection of a lung infiltrate or end of neutropenia. Primary efficacy parameter was the incidence of lung infiltrates until day 21 after initiation of chemotherapy. Secondary objectives were incidence of infections, length of stay in hospital, time to antifungal treatment, time to first fever, and drug safety. A total of 25 patients were randomly assigned to receive voriconazole (N=10) or placebo (N=15). Incidence of lung infiltrates until day 21 was 0 (0%) in the voriconazole and 5 (33%) in the placebo group (P=0.06). Average length of stay in hospital was shorter in the voriconazole group (mean 31.9 days) than in the placebo group (mean 37.3 days, P=0.09). Four patients were diagnosed with hepatosplenic candidiasis until a 4 week follow-up, all in the placebo group (P=0.11). Adverse events and toxicity did not differ between the two treatment groups. The trial was stopped prematurely when another trial demonstrated reduced mortality by antifungal prophylaxis with posaconazole, thus rendering further randomisation against placebo unethical. In AML patients undergoing induction chemotherapy, prophylactic oral voriconazole 200 mg twice daily resulted in trends towards reduced incidences of lung infiltrates and hepatosplenic candidiasis. Voriconazole was safe and well tolerated.

Hepatic candidiasis in a kidney transplant recipient treated successfully with amphotericin B and itraconazole

Keywords: Candida; hepatic candidiasis; kidney;liver; mycosis; transplantationThe incidence of hepatic candidiasis is difficultto estimate because of diagnostic difficulties. Itsfrequency was 7% in a study of 562 adult patientswith leukaemia [1]. Hepatic candidiasis (HC), alsoreferred to as chronic disseminated candidiasis,hepatosplenic candidiasis and granulomatous hepaticcandidiasis, affects almost exclusively patients under-going remission induction chemotherapy or bonemarrow transplantation for acute leukaemia [2].It occurs on recovery following prolonged episodesof bone marrow dysfunction and neutropenia [1].Theliver,spleenandsometimesthekidneysareinfectedwith Candida. Occasionally, patients with other typesof immunosuppression (aplastic anaemia, lymphoma,sarcoma or liver transplantation) may develophepatosplenic candidiasis [3]. This is the first reportedcase of HC in a kidney transplant recipient.

Protein C and S levels in acute leukemia

Patients with acute leukemia undergoing remission induction chemotherapy occasionally develop venous thrombosis despite severe thrombocytopenia and in the absence of disseminated intravascular coagulation. This observation prompted us to study the levels of the naturally occurring anticoagulant proteins C and S prospectively in patients undergoing remission induction chemotherapy for acute leukemia. Plasma samples from 50 adult patients with acute leukemia (34 AML, 16 ALL) were analyzed for protein C antigen, functional protein C, immunologic total and free protein S as well as levels of C4b binding protein (C4bBP). Plasma levels of immunologic protein C were significantly lower in patients with active acute myelocytic leukemia (mean = 77.9) than in controls (mean = 123.6) or patients in remission (mean = 132). Functional protein C levels were also significantly lower in AML patients with active disease (mean = 58.5) than controls (mean = 95.5) or patients in remission (mean = 98.5). Patients with acute lymphocytic leukemia (ALL) had normal levels of immunologic and functional protein C. Although total protein S levels were normal in all patients studied, levels of free protein S were significantly decreased in patients with active AML (mean = 29.3) compared with patients in remission (mean = 42.0) or controls (mean = 42.4). In contrast, patients with ALL, both with active disease and in remission had normal free protein S levels. This decrease in free protein S seen in active AML was not associated with liver disease, white cell count or an increase in C4bBP. These findings provide a possible explanation for the occasional occurrence of venous thrombosis in patients with acute myelocytic leukemia.

A rapid gas chromatographic method for the determination of plasma polyamines and its application to the prediction of tumour response to chemotherapy

Isobutyloxycarbonyl derivatives of the polyamines, spermidine, spermine and putrescine in 1 ml plasma were analysed on a mixed phase, 1.5% SE-30, 0.15% FFAP, column by temperature-programmed gas chromatography using a nitrogen-sensitive glass bead detector. Levels in 60 normal subjects (mean ±2 S.D.) were 0.13 ± 0.08 μmol/l for spermidine, 0.02 ± 0.04 for spermine and ⩽ 0.18 for putrescine. Elevated spermidine levels were found pre-treatment in only 20% of patients with advanced metastatic cancer, reflecting the lack of sensitivity of polyamines as markers for malignant disease. However, serial studies in 26 patients undergoing remission induction chemotherapy showed that a significant rise in plasma spermidine within 48 h correlated with subsequent clinical response ( p < 0.001). Tumour response to chemotherapy can be predicted by the assay of plasma polyamines.