Baseline Hb Level Research Articles

Prediction of the need for red cell transfusion in newly diagnosed ovarian cancer patients undergoing platinum-based treatment.

The objective of this study was to develop a predictive algorithm for the likelihood of red blood cell transfusion in women with ovarian cancer undergoing platinum-based chemotherapy. Patients in this analysis came from two phase III studies conducted by the Southwest Oncology Group and Gynecologic Oncology Group of platinum-based chemotherapy in advanced ovarian cancer patients, SWOG 8412 and SWOG 8501/GOG 104. The probability of packed red blood cell (PRBC) transfusion was modeled as a function of stage of disease, age, weight, creatinine clearance, hemoglobin (Hb) prior to the start of therapy, the platinum agent administered (i.e., cisplatin vs carboplatin), and the route of drug administration (i.e., intravenous vs intraperitoneal). Overall, 16% of patients developed at least grade 3 anemia (Hb < 8 g/dL) during primary chemotherapy, with 2% experiencing grade 4 anemia (Hb < 6.5 g/dL). PRBC transfusions were administered to 32% of patients. Factors that were determined to be predictive of PRBC transfusions were age and baseline Hb. In patients with bulky stage III or stage IV disease, the odds of transfusion increased by 66% for each 10-year increase in age and by 65% for each 1 g/dL decrease in baseline hemoglobin. Thus a patient aged 65 with a baseline Hb of 10.5 g/dL has approximately a 40% chance of transfusion. Older ovarian cancer patients (>65 years) with low baseline Hb levels (<10.5) at initiation of platinum-based chemotherapy are likely to become more anemic during treatment and should be considered for prophylactic erythropoietin therapy as an alternative to transfusion.

Chemotherapy-induced moderate to severe anemia in intermediate-grade non-Hodgkin’s lymphoma patients

This study investigated the incidence of anemia in chemotherapy-treated intermediate-grade non-Hodgkin’s lymphoma (IGNHL) patients. A historic case series design was used. The study data were obtained from 12 oncology practices that participated in the Oncology Practice Pattern Study (OPPS). The analysis focused on 353 IGNHL patients with normal baseline (prechemotherapy) hemoglobin (Hb) (≥12.0 g/dL). These patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone combination) therapy (at some point) from 1993 through 1999. Anemia was found to be prominent during chemotherapy. About 24% of the patients with a normal baseline Hb level dropped below 10.0 g/dL and 49% dropped to 10.0 -11.9 g/dL, at some point during chemotherapy. As anemia treatment data were unavailable, it is likely that some of these patients received therapy to boost their Hb levels, rendering our results conservative. A logistic regression model revealed that in patients with normal baseline Hb, age ≥60, female gender, lower baseline Hb level, and lymphoma histology classified as the Working Formulation (WF) E or H were significant predictors of a drop in Hb below 10.0 g/dL during chemotherapy. Chemo-therapy-induced anemia is frequently observed in lymphoma patients. It is possible to identify adverse baseline patient characteristics associated with higher risk of chemotherapy-induced anemia and carefully monitor such patients. Additional studies in community oncology practice are warranted to validate these findings and improve our understanding of the problems of anemia in chemotherapy treated non-Hodgkin’s lymphoma (NHL) patients.

Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis.

Both angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists reduce hemoglobin (Hb) levels in patients with posttransplantation erythrocytosis (PTE). However, their effects in transplant recipients without PTE are not certain, and the mechanism by which they reduce Hb levels in patients with PTE remains unclear. This study evaluated the effects of losartan and enalapril on Hb levels in relation to serum erythropoietin (EPO) and insulin-like growth factor-1 (IGF-1) levels in 8 patients with PTE and 10 patients without PTE. All 18 patients were treated sequentially with 24 weeks of losartan therapy, followed by 24 weeks of enalapril therapy; the two treatment phases were separated by a washout period. Patients with PTE showed significantly greater baseline Hb and IGF-1 concentrations compared with patients without PTE before both losartan and enalapril treatments. Baseline serum EPO levels were similar for patients with and without PTE. Baseline Hb level correlated significantly with IGF-1 level (r = 0.517; P = 0.002), but not with EPO level. Treatment with enalapril, 5 mg, reduced Hb levels more markedly than treatment with losartan, 50 mg, in patients with PTE. In patients without PTE, enalapril, 5 mg, mildly reduced Hb levels, whereas losartan, 50 mg, had no significant Hb-lowering effect. The reduction in Hb levels with enalapril therapy in patients with PTE was associated with a significant reduction in circulating IGF-1 levels, but not EPO levels, whereas losartan reduced Hb levels with no significant change in circulating IGF-1 and EPO levels. In patients without PTE, no significant change was noted in serum EPO and IGF-1 levels with either treatment. The differential Hb-lowering effect with losartan and enalapril treatment in patients with and without PTE suggests that the pathogenesis for PTE is complex and heterogeneous. Different erythropoietic mechanisms may be involved in patients with and without PTE. Further large-scale study is needed to determine the exact interaction between the renin-angiotensin system and regulation of IGF-1 and EPO synthesis and define the exact mechanism by which losartan and enalapril reduce Hb levels.

Predicting cancer-associated anaemia in patients receiving non-platinum chemotherapy: results of a retrospective survey

A 2-year retrospective chart survey of 1064 patients with colorectal, breast, lung or ovarian cancer, Hodgkin's disease, or non-Hodgkin's lymphoma was conducted at 24 centres in France to determine the prevalence of anaemia (haemoglobin (Hb) levels ⩽120 g/l) and need for transfusion in patients who received non-platinum-based chemotherapy for more than three cycles or 3 months. Baseline Hb levels documented anaemia in 37.1% of patients (all tumour types). By cycle 3, the prevalence of anemia increased to 54.1% of patients and remained over 50% at cycle 4. At some time during chemotherapy 14.5% of patients were transfused. Predictive risk factors for anaemia requiring transfusion included low baseline Hb, decrease in Hb during the first month of chemotherapy, primary tumour site, prior blood transfusions and duration of chemotherapy. By early identification of patients at the highest risk of developing anaemia, interventions such as epoetin alfa can be employed to reduce or eliminate the need for transfusions.

β‐thalassemia intermedia caused by compound heterozygosity for Hb Malay (β codon 19 AAC→AGC; Asn→Ser) and codons 41/42 (‐CTTT) β0‐thalassemia mutation

We report a case of β-thalassemia intermedia caused by compound heterozygosity for hemoglobin (Hb) Malay and codon 41/42 (-CTTT) β0-thalassemia mutation in a 38-year-old Chinese woman. This patient has long-standing anemia with a baseline Hb level of around 70 g/L. She worked as a full-time cashier and had not required regular blood transfusions. Nevertheless, she had splenomegaly necessitating splenectomy, cholelithiasis, and iron overload. This case illustrates the varied phenotypic expression associated with compound heterozygosity for Hb Malay and other β-thalassemia mutations. Since Hb Malay migrates as Hb A on electrophoresis and chromatography, this variant Hb mutation ought to be included in the differential diagnosis for β-thalassemia major or intermedia patients of Southeast Asian descent who are reported to have Hb A on the basis of Hb analysis. The possible presence of this mutation should also be considered in appropriate cases for genetic counseling in couples at risk of conceiving fetuses with β-thalassemia major or intermedia. Am. J. Hematol. 64:206–209, 2000. © 2000 Wiley-Liss, Inc.

β-thalassemia intermedia caused by compound heterozygosity for Hb Malay (β codon 19 AAC→AGC; Asn→Ser) and codons 41/42 (-CTTT) β0-thalassemia mutation

We report a case of beta-thalassemia intermedia caused by compound heterozygosity for hemoglobin (Hb) Malay and codon 41/42 (-CTTT) beta(0)-thalassemia mutation in a 38-year-old Chinese woman. This patient has long-standing anemia with a baseline Hb level of around 70 g/L. She worked as a full-time cashier and had not required regular blood transfusions. Nevertheless, she had splenomegaly necessitating splenectomy, cholelithiasis, and iron overload. This case illustrates the varied phenotypic expression associated with compound heterozygosity for Hb Malay and other beta-thalassemia mutations. Since Hb Malay migrates as Hb A on electrophoresis and chromatography, this variant Hb mutation ought to be included in the differential diagnosis for beta-thalassemia major or intermedia patients of Southeast Asian descent who are reported to have Hb A on the basis of Hb analysis. The possible presence of this mutation should also be considered in appropriate cases for genetic counseling in couples at risk of conceiving fetuses with beta-thalassemia major or intermedia.

Author reply

In their correspondence, Orhan and Yalçin raised some important issues with respect to the administration of prophylactic epoetin alfa to cancer patients receiving chemotherapy. Our cost-benefit analysis, as well as other economic evaluations using alternative methodology, have concluded that the general prophylactic use of this drug for all cancer patients receiving chemotherapy may not be cost-effective.1-3 Hence, in our article,1 we suggested that prophylactic epoetin alfa be considered only for selected patient subgroups who would be at high risk for requiring multiple blood transfusions. As described by Orhan and Yalçin, some of these subgroups may include patients with underlying renal, pulmonary, or cardiovascular diseases; older patients; those receiving cytotoxic chemotherapy; and patients who required multiple transfusions in the past. Even though risk factors for anemia have been reported in the literature,4 there has not been a prospective exploratory analysis to predict which cancer patients will likely require blood transfusions. Our group attempted to address this issue by conducting such an analysis with 100 cancer patients using retrospectively collected data.5 Using a multiple logistic regression approach with transfusion requirements (no vs. yes) as the outcome variable, baseline hemoglobin (Hb) level and cisplatin dose were identified as risk factors for future transfusions. Specifically, our model suggested that the need for transfusions increases by 28% for every 10 mg/m2 cisplatin dosage increment. With respect to baseline Hb, patients were 3 times more likely to receive a blood transfusion for every 1 g/dL drop in their prechemotherapy baseline Hb level.5 With these data, we subsequently developed a simple prediction model that could be applied in the clinic to identify patients likely to require transfusions. Once identified, the drug could also be administered to these patients a few weeks before the first cycle of chemotherapy, because it takes approximately 1 month for the drug's benefit to be realized.6 Hence, it may be cost-effective to restrict the use of prophylactic epoetin alfa to the high risk patients identified by the model. The prediction model for transfusion requirements that our group developed has limitations in that retrospective data were used in its development, the sample size was small, the data were obtained from a single center, and it has not been properly validated. Hence, what is required for ensuring that epoetin alfa is used in the most clinically and economically appropriate patient subgroup is the development of a prediction model based on high quality multicenter clinical trial data and with sufficient sample size. A similar instrument for predicting the survival of lymphoma patients has been successfully developed by the Non-Hodgkin's Lymphoma Prognostic Factors Group, which was able to create 4 patient risk groups with 5-year survival as the primary outcome.7 Through the application of Generalized Logit regression modeling,8 we envision a similar categorization of patients receiving cancer chemotherapy, but with need of blood transfusions (i.e., 0 vs. 1–2, 0 vs. >2) as the primary outcome. One practical way of achieving this objective would be to pool the available clinical trial data on epoetin alfa, use the appropriate statistical techniques to create a prediction model, and then validate the final product in the clinic. Our group would fully support such an initiative and would be eager to participate. In summary, epoetin alfa is an important adjunct therapy for patients receiving cancer chemotherapy, but it is not cost-effective to use it in a broad category of patients. The ability to identify which patients are likely to require blood transfusions would be an important step in ensuring that this high cost drug is used in the most clinically appropriate situations. George Dranitsaris M.Sc.Phm.*, * Pharmacoeconomic Research Program, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada

Recombinant Human Erythropoietin in the Anemia Associated With Multiple Myeloma or Non-Hodgkin’s Lymphoma: Dose Finding and Identification of Predictors of Response

Previous phase I-II clinical trials have shown that recombinant human erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a randomized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo. A total of 146 patients who had hemoglobin (Hb) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial. Patients were randomized to receive 1,000 U (n = 31), 2,000 U (n = 29), 5,000 U (n = 31), or 10,000 U (n = 26) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the patients, 84 suffered from MM and 62 from low- to intermediate-grade NHL, including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median serum Epo level was 32 mU/mL, and endogenous Epo production was found to be defective in 77% of the patients, as judged by a value for the ratio of observed-to-predicted serum Epo levels (O/P ratio) of < or = 0.9. An intention-to-treat analysis was performed to evaluate treatment efficacy. The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P = .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1,000 U, 2,000 U, 5,000 U, and 10,000 U groups, respectively (P values versus control). The probability of response (delta Hb > or = 2 g/dL) increased steadily and, after 8 weeks, reached 31% (2,000 U), 61% (5,000 U), and 62% (10,000 U), respectively. Regression analysis using Cox's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo, whereas only one quarter of those with adequate Epo levels did so. Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production. From a practical point of view, we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels, whereas the choice of the initial dosage should be based on residual marrow function.

234 Reduction of the risk of transfusion in patients with small cell lung cancer (SCLC) undergoing chemotherapy

This open-label, controlled, multicentre study examined the efficacy of subcutaneous (SC) Epoetin alfa (administered 3 times weekly) in preventing anaemia in 130 initially non-anaemic (Hb ≥ 10.5 g/dl) SCLC patients (pts) scheduled to receive 4–6 cycles of platinum-based combination chemotherapy. Patients were randomized to receive Epoetin alfa 300 IU/kg (group A, n = 44), 150 IU/kg (group B, n = 42) or no Epoetin alfa (group C). Treatment began 1 day after completion of the monthly chemotherapy cycle, and finished 3 days before initiation of the next cycle, for up to 6 cycles. Reductions in Epoetin alfa dose were made if Hb ≥ 15 gjdl. Logistic regression analysis of group C pts showed that low baseline Hb levels or a reduction in Hb level from higher baseline Hb levels, during the first cycle of chemotherapy, were important risk factors for transfusion. Group C required significantly more transfusions than Groups A and B (59%, 21%,45%, respectively; P ≥ 0.05). In addition, significantly more pts in group C experienced reduced Hb levels (Hb In conclusion, Epoetin alfa is effective and well tolerated in preventing anaemia and reducing the risk of transfusion in SCLC pts undergoing cyclic chemotherapy.

879 An epidemiological review of anaemia in cancer chemotherapy in Canada

The objective of this historical prospective review of 12 medical centres across Canada was to determine the prevalence of anaemia and the frequency of transfusion in patients (pts) receiving chemotherapy for the treatment of selected cancers (lung, breast, ovary, sarcoma Hodgkin's/non-Hodgkin's lymphoma, melanoma, bladder, colorectal). The 616 pts recruited had started chemotherapy in January–June 1992, continued to have treatment at regular intervals for at least 6 weeks (mean duration 24 weeks), and had received no chemotherapy within the previous 12 months. The pts were not treated with any investigational drug. Data collection finished 4 weeks after the end of the first chemotherapy regimen, to a maximum follow-up period of 26 weeks. A full multivariate analysis of transfusion and anaemia will be presented. Preliminary data indicate that 87 pts (14%) were transfused—72 (12%) for anaemia. In the different diagnostic groups (n>30), 4% of pts with colorectal cancer were transfused for anaemia (13% anaemic), compared with 5% of breast cancer pts (17% anaemic), 24% non-Hodgkin's lymphoma pts (53% anaemic), 25% ovarian cancer pts (51% anaemic), and 28% of lung cancer pts (52% anaemic). For all subjects, the mean baseline Hb level of pts not transfused was significantly higher than that of pts transfused for anaemia overall (12.8 vs 11.8 g/dl, <i>P</i><0.001), in the lung cancer sub-group (13.6 vs 12.7 g/dl, <i>P</i><0.05), and the ovarian cancer sub-group (12.1 vs 10.6 g/dl, <i>P</i><0.05). Overall, the mean nadir Hb level was also significantly higher in pts not transfused vs pts transfused for anaemia, and in the 5 sub-groups with n>30 (<i>P</i><0.001). The results of the full analysis, including stage of disease and chemotherapy regimen, will identify factors associated with anaemia and transfusion.