Recombinant human erythropoietin as adjuvant treatment for autologous blood donation in elective surgery with large blood needs (> or = 5 units): a randomized study

BACKGROUND: Autologous blood transfusion presents no infectious or immunologic side effects. The aim of this randomized study was to determine the impact of recombinant human erythropoietin (rHuEPO) on the donation of 5 units of autologous blood by nonanemic patients who were candidates for elective surgery with transfusion requirements of > or = 5 units. STUDY DESIGN AND METHODS: Starting on Day -35, 420 mL of blood was taken weekly. All patients received 200 mg of iron saccharose complex intravenously at each visit and six subcutaneous injections of rHuEPO (141 U/kg) or placebo between Days -21 and -7. RESULTS: Of 50 patients, 45 completed the study (placebo, 21; rHuEPO, 24). Total red cell production was higher in the rHuEPO group (p = 0.001). Donation of 5 units was possible for 67 percent (placebo group) and 79 percent (rHuEPO group) of patients (p = 0.5). The mean number of blood units donated was 4.6 (placebo group) and 4.7 (rHuEPO group). More patients in the placebo group received allogeneic blood (9/21 [43%] vs. 6/23 [26%]), although the difference did not reach significance (p = 0.34). CONCLUSION: In nonanemic patients donating 5 units of blood, rHuEPO associated with intravenous iron increased total red cell production. However, no difference was found between the rHuEPO and placebo groups with regard to the number of units of autologous blood donated of the number of patients receiving allogeneic blood transfusion.     

Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study

BACKGROUND: Blood transfusions are associated with higher postoperative morbidity and tumor recurrence rates in colorectal cancer surgery, To reduce the need for transfusions in patients with tumor-induced anemia who are not suitable for autologous blood donation, it was tested whether perisurgical erythropoietin application would be able to stimulate hematopoiesis adequately. METHODS: In a double-blind randomized study 150 IU/kg body weight erythropoietin was given subcutaneously every 2 days beginning 10 days before operation and continuing until postoperative day 2. Twenty patients were randomized into the erythropoietin group with three observed dropouts and 10 patients into the placebo group. RESULTS: In the erythropoietin group two episodes of hypertension and one deep venous thrombosis were observed. Preoperative hemoglobin response in the erythropoietin group (p = 0.069) was paralleled by a highly significant reticulocyte increase (p = 0.0004). However, frequency of blood transfusion was not different between both study groups (erythropoietin, 1.82 +/- 0.80 units/ patient; placebo, 1.80 +/- 0.97 units/patient). If iron availability was analyzed, a strong correlation between ferritin blood levels and transferrin iron saturation with hemoglobin response was observed in regression analysis (p < 0.001). CONCLUSIONS: These results indicate that hematopoiesis in anemic patients with colorectal cancer can be stimulated by erythropoietin; however, clinical efficacy is to be expected only in selected patients with high iron availability, which calls for further studies combining erythropoietin and parenteral iron application.     

Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly

OBJECTIVE: The purpose of the present study was to compare the dosage requirements of recombinant human erythropoletin (rHuEPO) administered subcutaneously (SC) either one or three times weekly. DESIGN: A randomized, prospective study. SETTING: The patients were recruited from two university hospitals and five county hospitals. PATIENTS: Thirty-three anemic patients on continuous ambulatory peritoneal dialysis (CAPD) treatment for end-stage renal failure completed the study. INTERVENTIONS: Initially, all were treated with rHuEPO SC three times a week until hemoglobin blood levels (Hb) remained constant between 105 and 121 g/L for three months. Following randomization, 17 patients continued the same treatment schedule (group A), while 16 patients received the same dose, but administered only once weekly for three months (group B). MAIN OUTCOME MEASURES: The Hb levels and rHuEPO doses at the start and at the end of the three-month study period. RESULTS: In group A the median Hb at randomization was 118 g/L (109-119) (25-75 percentiles) and, after three months, was 113 g/L (106-119) (p = 0.13), while in group B the median Hb was 114 g/L (108-119) and 114 g/L (106-120), respectively (p = 0.50). In group A the weekly dose of rHuEPO remained virtually unchanged during the study period, 65 (55-86) and 66.3 (55-95) U/kg/week, respectively, while in group B it was increased from 60.2 (46-88) to 77 (60-90) U/kg/week. The 22% increase (p = 0.03) took place during the last two weeks. CONCLUSIONS: Our findings indicate that a once-weekly SC dosing regimen of rHuEPO in anemic CAPD patients was equally effective in maintaining a stable hemoglobin level as a thrice-weekly dosing regimen.     

Three-dimensional appearance of Langerhans cells in human gingival epithelium as revealed by confocal laser scanning microscopy

Despite the reducing exposure to allogeneic blood in cardiac surgery, most of patients with anemia still require allogeneic blood. In this study, we have attempted to harvest the blood from cardiac patients with baseline hemoglobin levels below 11.0 g/dl using recombinant human erythropoietin (rHuEPO). 29 anemic patients undergoing cardiac surgery at our hospital between January 1994 and March 1997 were divided into two groups: 3 weeks' treatment with recombinant human erythropoietin (rHuEPO) and blood donation (group 1, n = 15) and iron supplementation alone (group 2, n = 14). There were no statistically significant differences among the two groups in patients characteristic and surgical data. No serious adverse events after phlebotomy were apparent in patients donating autologous blood. Patients in group 1 had significantly higher hemoglobin levels than patients in group 2 at 7 days before operation. The number of reticulocytes were increased at just before operation in group 1, whereas group 2 showed no significant increase. The estimated hemoglobin increase in group 1 were higher at 7 days and just before operation. In 75% of group 1, allogeneic blood transfusion could be avoided, while all patients in group 2 received allogeneic blood transfusion. This study suggests that the combination of rHuEPO administration and autologous blood donation would be beneficial for anemic patients in elective cardiac surgery. The use of rHuEPO should not be restricted to anemic patients.     

Resuscitation from hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, or hetastarch

BACKGROUND: An oxygen-transporting hemoglobin solution should be more effective than a nonhemoglobin solution for resuscitation from hemorrhagic shock. A way to evaluate this effectiveness is to determine whether a hemoglobin solution can reverse the base deficit accumulated during hemorrhage at a faster rate than a nonhemoglobin solution. Using this criterion, we compared the resuscitative powers of autologous blood, hetastarch (Het), and diaspirin cross-linked hemoglobin (DCLHb). METHODS: Fifteen sedated, spontaneously breathing sheep (37.5 +/- 10.2 kg) were bled until base deficits fell to -5 to -10 mEq/L, and plasma lactate concentrations rose to 6 to 9 mg/L. The animals were resuscitated with autologous blood (n = 5), Het (n = 5), or DCLHb (n = 5) (3.5-4.0 mL/kg every 15 minutes) until base deficits returned to prehemorrhage baseline. RESULTS: Exsanguination to target base deficits required removal of an average of 41.4 +/- 5.5 mL blood/kg (estimated total blood volume, 80 mL/kg). Resuscitation required 18 +/- 3, 38 +/- 2 (different from blood), and 35 +/- 1 (different from blood) mL/kg of autologous blood, Het and DCLHb, respectively, over periods of 78 +/- 8, 163 +/- 10 (different from blood), and 129 +/- 9 minutes (different from blood and different from Het (p < or = 0.05)). Based on regression analysis, autologous blood, Het, and DCLHb corrected the base deficit at rates of, respectively, 0.074 (different from Het (p < or = 0.05)), 0.016, and 0.056 (different from Het (P < or = 0.05)) mEq/L/min. CONCLUSIONS: Based on the rate of base deficit correction and the volume of solution required, autologous blood was the most effective resuscitation solution. However, DCLHb was more effective than Het. DCLHb may be an attractive alternative to blood for resuscitation from hemorrhagic shock.     

Is beta-carotene an antioxidant?

The clinical efficacy of s.c. erythropoietin (EPO) injected subcutaneously once weekly was compared in patients (median age of 63 years) on peritoneal dialysis (PD, n = 19) and in haemodialysis (HD, n = 13). The blood haemoglobin prior to start of EPO was not significantly different between the groups. The mean (+/- SD) dose of EPO given to achieve a blood haemoglobin level of 100 g/l was not significantly different between the PD and the HD-responders (85 +/- 45 units/kg body weight and week, versus 112 +/- 33, respectively). Significantly more patients using PD than in HD achieved a haemoglobin level > or = 95 g/l (p = 0.02). The HD group had significantly higher ferritin values. Serum iron and intact PTH were not different between the groups. In conclusion, s.c. EPO injections once, or occasionally twice, weekly increased blood haemoglobin levels in a greater proportion of patients on PD than in those on HD.     

Thickened gastric mucosal capillary wall: a histological marker for portal hypertension

We investigated the efficacy and safety of subcutaneous recombinant human erythropoietin (rHuEpo) in 25 children with chronic renal allograft dysfunction (13 girls, 12 boys, mean age 15.8 +/- 4.2 years) for a treatment period of 9-162 (median 43) weeks. rHuEpo was started once weekly at a dose of 105 +/- 25 U/kg per week in 16 children, twice weekly at a dose of 175 +/- 70 U/kg per week in 6 children, and three times weekly at a dose of 270 +/- 28 U/kg per week in 3 children. The hematocrit increased in 21 children from 23.2% +/- 3.1% to 33% +/- 3.1% within 7.2 +/- 4.9 weeks at a mean rate of 1.98%/week. The hematocrit increase and rHuEpo starting dose were linearly related (delta hematocrit/week = 0.8+0.08 U/kg per week, r = 0.44, P < 0.05). The maintenance dose was 74 +/- 23 (43-114) U/kg per week. Four children failed to reach the target hematocrit, most likely due to noncompliance. Seventeen recurrences of anemia ("anemic episodes") during rHuEpo therapy were identified in 12 children, mostly associated with acute or insidious deteriorations in graft function. There was no acceleration of progression of graft dysfunction with rHuEpo treatment. We conclude that subcutaneous rHuEpo at a single weekly dose of 100 IU/kg per week is highly effective in children with chronic graft dysfunction. Children who appear to be rHuEpo resistant or experience rHuEpo-resistant episodes should be assessed for noncompliance, changes in graft function since the last dosage adjustment, and blood loss, such as seen in dysfunctional uterine bleeding in adolescent girls.     

Efficacy of oral iron supplementation is not enhanced by additional intravenous iron during autologous blood donation

BACKGROUND: The study compared the efficacy of oral iron combined with intravenous iron supplementation to that of oral iron supplementation alone in increasing the preoperative production of hemoglobin (Hb) in autologous blood donors with normal iron stores. STUDY DESIGN AND METHODS: One hundred eight iron-replete patients who were scheduled for donation of 3 units of autologous blood at weekly intervals were randomly assigned to receive, in a double-blind fashion, no iron supplementation (placebo, Group 1), oral iron supplementation (285.6 mg of elemental iron/day, Group 2), or oral iron plus intravenous iron supplementation (285.6 mg of elemental iron/day orally plus 102.5 mg of elemental iron/week intravenously, Group 3). The amount of Hb produced during the 21-day study period was determined by the total amount of Hb donated minus the change in the amount of circulating Hb between the first donation (Day 0) and the poststudy examination (Day 21). RESULTS: Hb production did not differ significantly in the two iron-supplemented groups (oral iron, 85 +/- 36 g; oral plus intravenous iron, 74 +/- 43 g). The patients in the oral iron group produced a significantly greater amount of Hb than those in the placebo group (85 +/- 36 g vs. 52 +/- 41 g, p < 0.01). CONCLUSION: Oral iron supplementation increased the production of Hb in autologous blood donors more than placebo did. Additional intravenous iron did not lead to a further increase in preoperative Hb production.     

Computed tomography of the head by the accident and emergency department--why 24 hour access is vital

A 50-year-old man was admitted to our hospital for possible surgery. Echocardiogram showed severe calcification of the aortic valve, and cardiac catheter examination recorded a gradient greater than 150 mmHg across the valve. These results determined aortic valve replacement (AVR) to relieve the pressure-overloaded ventricle. Preoperative evaluations however, demonstrated anemia derived from hereditary spherocytosis (HS), an inherited hemolytic disorder. In order to avoid homologous blood transfusion, the following strategies were tried; 1) an iron supplement and an injection of recombinant human erythropoietin (rHuEPO); 2) pre- and perioperative autologous blood transfusion; and 3) an aggressive iron supplement just after the surgery. These raised the blood hemoglobin concentration to the criterion where autologous blood donation was started, and maintained the hemoglobin level stable, up to his discharge. In conclusion, bloodless cardiac surgery is possible for cases with anemia, and some strategies should be tried to raise and maintain the blood hemoglobin concentration well.     

Epoetin alfa. A bloodless approach for the treatment of perioperative anemia

Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.     

Erythropoietin stimulates testosterone production in man

Human recombinant erythropoietin (rHuEPO) treatment improves sexual function in end-stage renal failure patients with a still-debated mechanism. Experimental data suggested that rHuEPO was able to stimulate rat Leydig steroidogenesis; therefore, it has been suggested that rHuEPO may induce its effects in humans by acting on gonadal steroid production. Thirteen young adult males (age range, 16-28 yr) catheterized at peripheral and left internal spermatic venous levels during a contrast study for varicocele, were studied. In five subjects, rHuEPO (60 IU/kg, up to a maximum of 4000 IU total) was injected over 1 min in the cubital vein. Similarly, in other five patients, 50 micrograms GnRH were infused. In three subjects, 2 mL saline were injected, as controls. Plasma LH, FSH, and testosterone (T) levels were then determined at -15, 0, 15, 30, 45, 60, 90, and 120 min simultaneously in peripheral and spermatic venous blood. rHuEPO infusion did not have any effect on plasma LH and FSH levels in peripheral or spermatic veins. Similarly, rHuEPO infusion did not affect peripheral T concentration, but increased (approximately 400% vs. controls; P < 0.05) spermatic T levels. GnRH infusion induced an increase in plasma LH and FSH levels in both peripheral and spermatic veins. After GnRH infusion, an increase of approximately 12-fold (P = 0.05-0.001) in T was observed only at the spermatic venous level, without any peripheral T variation. These findings show that rHuEPO was able to influence testicular steroidogenesis by stimulating T production in man, whereas the absence of any effect on gonadotropin secretion suggests that rHuEPO might act directly on human Leydig cell function.     

Low-dose subcutaneous recombinant erythropoietin in children with chronic renal failure. Australian and New Zealand Paediatric Nephrology Association

In a multicentre trial, low-dose subcutaneous recombinant human erythropoietin (r-Hu EPO) was evaluated in 22 children aged 4 months to 16 years with anaemia of chronic renal failure over a 12-month period. A starting dosage of 50 U/kg twice weekly was given until a target haemoglobin of 9-11 g/dl was achieved. The dosage was increased by 50 U/kg per week, each 4 weeks, if the haemoglobin did not increase by 1 g/dl per month. When the target haemoglobin was achieved, the same weekly dosage was given as a single injection. After 10 weeks, the mean haemoglobin increased from 6.7 +/- 0.7 to 9.6 +/- 1.9 g/dl (P < 0.001) and the haematocrit from 19.8% +/- 2.4% to 29.3% +/- 6.3% (P < 0.001). By 4 months the target haemoglobin was achieved in 19 patients on 50 U/kg twice weekly and 1 patient on 75 U/kg twice weekly. Two children with severe renal osteodystrophy failed to respond to 95 U/kg and 150 U/kg twice weekly. The maintenance weekly dose of r-Hu EPO in 9 children over 4-12 months ranged between 45 and 125 U/kg. The Wechsler intelligence score increased in 11 children from 92 +/- 16 to 97 +/- 17 over the 12-month period (P = 0.007). No adverse effects were recorded. A starting dose of r-Hu EPO of 50 U/kg subcutaneously twice weekly is recommended as effective and safe for the majority of children with anaemia of chronic renal failure.     

A population pharmacokinetic study of alminoprofen penetration into synovial fluid

BACKGROUND: Transfusing fresh autologous blood during cardiac surgery may improve hemostasis and decrease the need for transfusion. STUDY DESIGN AND METHODS: A prospective randomized study was performed with fresh whole blood (WB) obtained by intraoperative hemodilution (IH) and with platelet-rich plasma (PRP) obtained by perioperative apheresis from adult cardiac surgery patients. RESULTS: Seventy patients were randomly assigned to three arms: 24 to the PRP arm, 18 to the IH arm, and 28 to serve as controls. A mean of 924 +/- 130 mL of WB was collected from the IH group, and a mean of 650 +/- 124 mL of PRP was collected from the PRP group (mean, 1.42 +/- 0.74 x 10(11) platelets); these components were transfused after bypass. Preoperative measures were similar among groups. Intraoperatively, the groups did not differ in bypass time, estimated blood loss, number of transfusions, or proportion receiving transfusion(s). Postoperatively, control patients had more mediastinal drainage (736 mL vs. 476 mL [IH] and 463 mL [PRP]; p = 0.014), but there was no difference in the proportion of patients requiring red cell transfusion (p = 0.87), the hemoglobin at discharge (p = 0.20), or the length of hospitalization (p = 0.57). CONCLUSION: Although a hemostatic benefit manifested as reduced postoperative bleeding was observed, this study does not support the use of fresh blood components obtained by IH or PRP collection during low-risk cardiac surgery. Additional studies are needed to assess whether more aggressive component collection or the use of these techniques in high-risk cases may have a greater impact on clinical outcome variables, including transfusion.     

The effect of subcutaneous recombinant human erythropoietin (r-HuEPO) on anemia in cancer patients receiving platinum-based chemotherapy

Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy.     

Early and late effects of erythropoietin on glucose metabolism in maintenance hemodialysis patients

The effects of recombinant human erythropoietin (rHuEPO) on the glucose metabolism were evaluated by intravenous glucose tolerance test in 20 maintenance hemodialysis patients. In 8 cases the glucose tolerance tests were performed before and after a single intravenous injection of 50 IU/kg of rHuEPO and in 12 cases before and after 3 months of rHuEPO therapy at doses of 50 IU/kg three times/week and 2 weeks after rHuEPO withdrawal. For each test glucose, immunoreactive insulin (IRI) and C peptide (C-p) plasma values were measured, and glucose constant decay, whole IRI (area IRI) and C-p area C-p) production, insulinogenic index, and insulin resistance index were calculated. After 3 months of rHuEPO therapy, the glucose constant decay increased significantly, area IRI, area C-p, and insulin resistance index decreased significantly, and the insulinogenic index did not change. No correlations were found between changes in hemoglobin values and changes in glucose metabolism parameters. Acute rHuEPO administration and rHuEPO withdrawal had no effect on glucose metabolism, despite significant changes in plasma erythropoietin levels. Long-term rHuEPO therapy improves glucose metabolism in maintenance hemodialysis patients significantly, mainly by reduction of insulin resistance. Neither anemia correction nor a direct effect of rHuEPO on some metabolic steps seem to be responsible of these effects.     

Effect of blood conservation in open-heart surgery: a comparison of 3 different methods

Conventional blood conservation techniques have been insufficient to decrease blood transfusion requirement in open-heart surgery. Blood conservation and erythropoietin administration were performed to avoid homologous blood transfusion. Intraoperative autotransfusion has been routinely used in cardiac operations with cardiopulmonary bypass in our hospital. To evaluate the effect of conservation techniques, 286 patients were divided into four groups. In group I (23 patients), autologous whole blood was drawn and saved one to two weeks before operation. In group II (50 patients), erythropoietin preparation was given subcutaneously once a week and autologous blood conservation was also performed in the same manner as group I. In group III (48 patients), intra-operative hemodilutional autologous blood transfusion was performed. In group IV, as a control group (165 patients), only intra-operative autotransfusion was used. Homologous blood transfusion was avoided in 83% of group I patients, in 90% of group II, in 82% of group III, and 29% of group IV. In addition, in group II the hemoglobin value at the time of discharge was significantly higher than those of other groups (p < 0.05-0.01). Thus, conventional blood conservation techniques plus subcutaneous administration of erythropoietin was very effective to increase the rate of "non-blood" open-heart surgery.     

Polymorphisms of the human beta-defensin-1 gene

Erythropoietin (EPO) plasma levels were monitored during the perioperative period in 61 consecutive patients (22 males - 39 females), aged 62.5 +/- 9.5 years, scheduled for hip arthroplasty. All patients underwent intraoperative blood salvage (IOBS) and were subdivided into three different groups according to their hemoglobin levels (Hb) 24 hours postoperatively (group A: Hb < 8 g/dl; group B: Hb between 8-9 g/dl; group C: HB > or = 9 g/dl). Seventy-two hours after surgery EPO levels were significantly different in group A (135 +/- 68) compared to group C (54.3 +/- 32), with a positive correlation (p < 0.01) between Hb and EPO levels. On the basis of these results we suggest that a programmed autologous red blood cell collection aimed at obtaining the lowest hemoglobin values during the first 24 hours after surgery, may be of clinical utility in preventing homologous blood needs.     

Ethnic disparities in patient recall of physician recommendations of diagnostic and treatment procedures for coronary disease

A pilot study was performed to determine the efficacy of 13-cis-retinoic acid (CRA) and alpha-tocopherol (AT) with increasing doses of recombinant human erythropoietin (rHuEPO) in anemic patients with primary myelodysplastic syndrome (MDS), to determine response rate and to determine the dose requirement and long-term effects of rHuEPO therapy on the transition to acute non-lymphocytic anemia and survival of these patients. Twenty-four consecutive MDS patients were entered into the study. Patients were stratified according to their FAB classification at study entry. Therapy consisted of a 6 month trial of CRA (100 mg m(-2) day(-1) and AT (800 mg day(-1)) with rHuEPO (150 units kg(-1) body weight subcutaneously three times a week). The rHuEPO dose was escalated to daily doses at 2 months, and 300 U kg(-1) body weight given three times a week for another 2 months and continuing therapy after 6 months in responsive patients. Response was measured by elimination of transfusions requirement (partial response, PR) and normal hemoglobin level and complete blood counts (complete response, CR). Observed responses for the 23 evaluable patients were 2 CR and 6 PR (34.8%). Odds ratio analysis showed that patients with anemia alone were 14 times more likely to respond than patients with pancytopenia (p = 0.06). In our study, two patients (8%) transformed to acute leukemia in CRA + AT + rHuEPO-treated patients. Median survival of 34 months with a median follow-up of 17 months (range 3-70 months) was observed. The response rates with the addition of rHuEPO to CRA and AT was similar but occurs earlier at 2 months compared to 6-10 months with CRA and AT alone and did not alter survival. There was no increase in the risk for leukemia in the group treated with rHuEPO. Response to either therapy appeared to be limited to patients in the early stages of MDS.     

Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease

Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.     

Preoperative autologous blood donation in patients with malignant tumors of the head and neck region

Twelve instances of preoperative autologous blood donation were assessed in 10 patients with malignant tumors of the head and neck region. All patients received preoperative radiation therapy and chemotherapy and most of the cases were also given recombinant human erythropoietin (EPO) and iron sulfate. Hemoglobin concentrations immediately before starting the 800ml blood donations were higher than 13g/dl in 5 cases and less than 13g/dl in 6 cases. The mean hemoglobin concentration just prior to donation and one week after donation in these two groups changed from 14.4g/dl to 12.5g/dl and 11.7g/dl to 11.7g/dl, respectively. A 1000ml blood donation was carried out in only one patient, and the hemoglobin concentrations just before donation and one week after donation were 11.4g/dl and 10.5g/dl, respectively. Only half of the blood volume scheduled, 400ml, was achieved in 3 of the 12 cases attempted because of fever, diarrhea and a change of the day of surgery, respectively. The mean estimated blood loss in the 10 patients that underwent surgery as planned was 898ml, and allogenic blood transfusion was avoided in all cases. We concluded that 800-1000ml preoperative autologous blood donation can be performed safely in patients with advanced malignant tumors of the head and neck region who have undergone preoperative radiation therapy and chemotherapy by giving EPO and iron sulfate.