Journal of Surgical Oncology 43:19-23 (1990)

Autologous Transfusions for Cancer Patients Undergoing Elective Ablative Surgery BENJAMIN LICHTIGER, MD, PhD, YANG 0. HUH, MD, MARGIE ARMINTOR, MT (ASCP), AND HARALD E. FISCHER, MU, PhD From the Section of Transfusion Medicine and Laboratory Immunology, Division of Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston

Patients who have cancer are exposed to the adverse consequences of blood transfusions, such as transmissible diseases. This study presents an examination of a program of autologous blood deposit for cancer patients undergoing elective surgical procedures. Over a 3-year period, 235 patients deposited 388 units of autologous blood: 6 for head and neck tumor surgery, 8 for neurosurgical tumors, 8 for gastrointestinal and colorectal tumor surgery, 14 for adrenal tumor surgery, 16 for gynecologic tumor surgery, 23 for soft tissue and bone tumor surgery, 25 for mastectomies and reconstructive breast surgery, 42 for genitourinary tumor surgery, and 93 for bone marrow aspirations for autologous transplants. One hundred eighty-two patients (77.4%) used 278 units (71.6%) of their autologous blood units during the operations, 50/182 required additional homologous blood, and 53 did not require transfusions with autologous blood. Our study shows that a majority of these patients ( 1 321182) underwent surgery using only autologous transfusions. Therefore, we believe that predeposited autologous blood is a viable alternative to homologous blood for cancer patients undergoing surgery. KEY WORDS: transfusion transmitted infectious diseases, cancer surgery, predeposited blood, alteration of immune responses

INTRODUCTION Autologous blood is undisputably the safest blood available to the patient undergoing elective surgery [ 11. Autologous blood predeposit programs are now available for almost any type of elective surgery in which the perioperative transfusion of blood is anticipated [2,3]. However, patients with cancer, who are scheduled for elective ablative surgery are not routinely offered the option of using their own predeposited blood, perhaps because of misconceptions that cancer patients, unlike others, would not derive any benefits from the use of autologous blood. Nevertheless, cancer patients undergoing elective surgery do require blood transfusions. They are also affected by transfusion-transmitted infectious diseases, which often have grave consequences for their therapeutic management and prognosis. In addition, cancer patients have become more involved in making decisions 0 1990 Wiley-Liss, Inc.

about their therapy options and have started to demand that autologous blood deposit programs be made available to them. In view of these facts and recent information that homologous blood products may induce profound, although temporary, immunologic dysfunctions [3], we have developed and implemented an autologous blood predeposit program at The University of Texas M.D. Anderson Cancer Center for all cancer patients undergoing elective procedures that would otherwise require the use of homologous blood products. Our report shows that patients undergoing ablative

Accepted for publication September I I , 1989. Address reprint requests to Benjamin Lichtiger, M.D., Ph.D., Chief, Transfusion Medicine and Laboratory Immunology, U.T.M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 7, Houston. T X 77030.

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Lichtiger et al.

TABLE I. Autologous Blood Deposit and Use by Type of Surgery

Type of surgery

No. of patients

Headineck surgery

6

Neurosurgery

8

Gastrointestinal/ coiorectal surgery Adrenal surgery

X

Gynecologic surgery Soft tissueibone surgery Mastectoiniesi breast reconstructions Genitourinary surgery Bone marrow aspirations Total

14

16 23 25 42 93

235

Mean (range) of EBL"

Units of Units of No. of No. of autologous autologous Units of patients patients Units of blood Units (%) blood homologous transfused transfused autologous deposited of transfused per blood 30 days 30 days blood per patient: autologous patient: transfused before after deposited mean (range) blood used mean (range) penoperatively surgery surgery

25 1 (30-650) 170 (55-300) 1,025 (250-2,450) 855 (100-5,000) 400 (75-1,lOO) 440 (3-1,500) 240 (lo-550) 1,400 (S0-3,600) 976.7 (500-1,500)

9

8 14

1.5 (1-3) 1

4(44)

I .75

0

0

0

0(0)

0.6 (0-2) 0

0

0

0

1 l(79)

1.375

5

I

2

I .36 (0-5)

2

0

I

1

0

0

0

4

0

1

3

0

2

37

0

5

31

IS

30

82

16

41

26

(1-3) 2.I4 (1-5) 1 .5

35

(1-4) 1.52

15(43)

27

(1-3) 1.08

I l(41)

30

(1-3)

I9(63) 1 l(42)

(0-1)

( 1-21

97 142

2.5 (1-5) 1.52 (1-3)

388

(0-2) 0.65 (0-2) 0.44

73(75) I34(94)

1.8 (0-4) 1.44 (1-2)

278(72)

"EBL. Estimated blood loss, in ml, for the surgical procedure

cancer surgery benefited most from this program because very few were subsequently exposed to additional homologous blood products. In contrast, cancer patients undergoing bone marrow aspirations (BMA) for autologous transplantation received numerous homologous blood products both pre- and post-BMA. Thus, their predeposit of autologous blood produced little benefit beyond freeing homologous blood products for transfusion to other cancer patients.

MATERIALS AND METHODS Patient Population From January 1 , 1985 through August 31, 1988, a total of 235 patients donated at least one unit of autologous blood before undergoing elective surgery. The patients' ages ranged from 14 to 75 years. One hundred thirty-three patients were male, and 102 were female. One hundred forty-two of the patients were scheduled to undergo various elective surgeries for cancer ablation (Table I). An additional 93 patients who had various primary hematologic diseases and were undergoing multiple BMA for autologous transplantation were also included in this study because they were classified as routine surgery patients, and the procedure was performed in the operating room. BMA patients are routinely transfused with two or three units of blood during the procedure.

Patient Criteria for Autologous Blood Deposit Program Admission Patients are referred to the autologous blood deposit program by their physicians, who make written requests in patients' medical charts, and the Transfusion Medicine Physician (TMP) evaluates the patient-candidates for autologous blood deposit. Data provided to the TMP include the type and date of surgery and the expected amount of blood needed for the operation. The TMP evaluates the patient based on the pertinent information in the medical chart, including electrocardiogram results, hematologic status, and history of bleeding tendency, major heart disease, and seizure disorders. Age is not considered a limiting factor as long as the patient has peripheral venous access for phlebotomy. Patients undergoing chemotherapy or antibiotic treatment are temporarily deferred until the therapy is completed. At the time of each donation, the patient's vital signs and hematocrit or hemoglobin level are checked. The vital signs should be within normal limits. The hematocrit level should be 34% or greater at each phlebotomy, or the hemoglobin level should be 1 1 gidl or greater. In rare cases where the patient's condition allows and other factors are acceptable, a patient with a 30% hematocrit level may also deposit blood, if the procedure is discussed with the attending physician and the risks are explained to the patient.

Autologous Transfusions for Cancer Patients

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TABLE 11. Patients Transfused With Autologous Blood Only, Autologous and Homologous, and Not Transfused Type of surgery

No. of patients

Bone marrow aspirations Genitourinary surgery Mastectomiesibreast reconstructions Soft tissue/bone surgery Gynecologic surgery Adrenal surgery Gastrointestinalicolorectal surgery Neurosurgery Headineck surgery Total

93 42 25 23 16 14 8 8 6 235

Autologous & homologous blood patients (%)

Not transfused patients (%)

(70.96) (64.39) (28.0) (26.1) 10 (62.5) 10 (71.4) 6 (75.0) 0 0

27 (29.03) 12 (28.6) 2 (8.0) 5 (21.7) 0 2 (14.3) 2 (25.0) 0 0

0 3 (7.1) 16 (64.0) 12 (52.2) 6 (37.5) 2 (14.3) 0 8 (100.0) 6 (100.0)

132 (56.17)

50 (2 I .27)

53 (22.56)

Autologous blood only patients (%) 66 27 7 6

Phlebotomy Scheduling The schedule of phlebotomies is flexible to accommodate the patient’s needs concerning logistics and hospital readmittance, especially if the patient is from out of state. Blood is drawn and predeposited as many as 2 or 3 months or as little as 1 day before surgery. If the risks to the patient are considered acceptable and the timing for donation is convenient, the first unit is obtained in standard fashion immediately after the patient signs the appropriate consent form. A note is made in the progress section of the patient’s chart. Depending on the number of units required for a particular operation, the patient’s hemoglobinihematocrit level, and the patient’s clinical condition, blood is usually drawn on a weekly basis, although it can be taken two or three times per week if necessary. Based on the date of surgery, the TMP decides whether the blood should be stored as whole blood, packed red blood cells with fresh frozen plasma, or frozen red blood cells and fresh frozen plasma. On the day of surgery, the autologous blood units are issued to the operating room as requested by the surgeon. Autologous blood units that are not transfused to the patient are left to expire on the shelf; neither the autologous blood nor any of its components is transfused to patients other than the one who donated it. Blood Testing The units of blood obtained in the autologous blood donation program are ABO-grouped and Rh-typed and fully screened as any routine homologous donation. Each unit is then labeled accordingly in compliance with the requirements of regulatory and accrediting agencies (American Association of Blood Banks, College of American Pathologists, Food and Drug Administration). In addition, each unit has a bright red label that says “Autologous Blood” in bold ietters, which indicates the patient’s name and identification number.

RESULTS A total of 388 units of autologous blood was predeposited by 235 patients undergoing elective surgical pro-

cedures (Table I). One hundred forty-two of these units (36.6%) were donated by 93 BMA patients. Fifty-three of the 235 patients (22.56%) did not receive their autologous or any homologous blood perioperatively (Table 11). The remaining 182 patients (77.4%) were transfused with 278 units of autologous blood (7 1.9% of units). Eighty-two additional units of homologous blood were transfused to 50 patients (21.27%). Of these patients, 27 underwent BMA and received 31 of the 82 units (37%) of homologous blood. The patients who had ablative surgery and required homologous blood were primarily those with genitourinary tumors; 37 of the 82 (45%) homologous blood units were transfused to 12 patients in this group.

DISCUSSION Autologous transfusions offer the patient the safest blood in terms of disease transmissibility, potential alloimmunization, transfusion reactions, and other adverse effects [4]. A considerable body of documentation now exists showing that homologous blood transfusions induce a state of immune dysfunction that may last for years [4]. Increased frequency of cancer recurrence, perioperative bacterial infections, and worsened outcome of patients infected with human immunodeficiency virus (HIV- 1) has been associated with transfusions of homologous blood and plasma. The observations in human subjects have been thoroughly documented in controlled animal studies where a plethora of immune functions could be serially monitored and analyzed in subjects receiving homologous blood transfusions. The animal data accrued point out without any question that vital immune functions are definitely altered on a discernible short temporary basis [4]. In view of the current body of information, it could be assumed until definite evidence is elicited that homologous transfusions may have deleterious immunologic consequences in cancer patients. In the present study, we have demonstrated that cancer patients undergoing elective ablative surgery can actively

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Lichtiger et al.

and efficiently participate in an autologous blood predeposit program. Minor logistics modifications or adjustments of the donor criteria can provide the participating patient with not only his own packed red blood cells but also autologous fresh frozen plasma; also, if the time between donation and transfusion allows, whole blood can be used. Patients undergoing BMA for various hematologic malignancies also can only temporarily derive benefits from this program. These patients usually have received multiple transfusions of different blood products before the BMA and continue to receive them long after. The autologous predeposit program provides the patient undergoing BMA little benefit besides the feeling of actively participating in the management of their disease. Tables 1 and I1 clearly show that patients requiring additional homologous blood units were those whose surgeries had high estimated blood losses (EBLs). Patients undergoing similar surgical procedures who did not avail themselves of the autologous blood deposit program received transfusions in similar numbers and volumes as those who used the predeposit option (data not shown). Table I also shows, however, that the patients whose surgeries had large EBLs also used their predeposited blood at the highest rate. In contrast, patients with lower EBLs only used 44% of their predeposited blood. This pattern suggests that the amount of blood deposited should be calculated more precisely, if possible, to meet the patients’ needs. In our experience, patients are unquestionably much more concerned about their prospective transfusions now than they were several years ago. Unquestionably, homologous blood transfusions carry the risk, however, minuscule, of transmitting infectious viral diseases such as hepatitis B , Non-A, Non-B hepatitis, HIV-I, et al. Although all donors are carefully screened and the blood is extensively tested, the evidence of post-transfusion transmitted viral diseases is still a distinct possibility. Recent publications have documented that non-A, non-B hepatitis may affect 38% of all transfused patients in the United States. These percentages exist in spite of all the precautions taken to exclude donors in high-risk life styles and the introduction of surrogate testing of donated blood [ S ] . Post-transfusion HIV infection also poses a potential but distinct possibility for the recipient of a transfusion. The calculated risk of transfusion of an HIVinfected unit of blood has been estimated to be in the range of 1/ 100,000, despite the various rigorous testing procedures. This may happen at an early state of infection of the blood donor when the HIV-I antibodies are not present or are at such low levels that they are not detectable with the currently used test methods [6]. These factors clearly underscore the obvious advantages of autologous over homologous blood.

Informational sources in the lay literature [7] have made the patient-consumer aware of this option. Consequently, we have concluded that the initial impetus for the option of autologous blood donation was driven by the demands of patients rather than those of physicians. Despite the fact that the U.T.M.D. Anderson Cancer Center transfusion service actively pursued an autologous blood predeposit program in the past, it was not until a great number of patients started demanding autologous transfusions, fearing transfusion-associated acquired immunodeficiency syndrome, that the program acquired significance and started to involve the attending physicians, as well. Although current guidelines recommend that the units of blood be drawn at least 3 days apart and no later than 72 hours before surgery [8], we have adapted this schedule to accommodate some patients. Of the 235 patients, 35 (14.9%) had the last unit of autologous blood drawn the day before the surgical procedure and did not suffer any resultant adverse effects during the operation. The most important limiting factor in collecting the units of autologous blood needed for the scheduled surgery was, in general, the inadequate time left between the day the decision to operate was made and the operation date. This reason alone forced us to use homologous blood to meet some patients’ needs. In our experience, given enough time, patients could depend on homologous blood at a significantly diminished level. In conclusion, we have shown that the autologous predeposit of blood is a viable option for patients undergoing ablative cancer surgery, using the same or similar donor criteria and phlebotomy approaches as those used for patients undergoing other kinds of surgery. Because patients today more clearly understand their blood transfusion options, they increasingly demand that an autologous blood donation program be made available to them, even if they later might have to depend on homologous blood components, as did the BMA patients we studied. Because the use of autologous blood decreases a patient’s exposure to potential risks from homologous blood, we feel programs such as these should be made available on a widespread basis. Further research is needed to make the predeposit of blood more efficient and more fully meet the needs of the patients who participate in these programs.

REFERENCES Nicholls MD, Janu RM, Davies JV, et al.: Autologous blood transfusion for elective surgery. Med J Aust 144:396-399, 1986. Swanson DA, Lo RK, Lichtiger B: Predeposit autologous blood transfusions in patients undergoing irradiation and radical cystectomy. J Urol 1305392-894, 1983. Council on Scientific Affairs: Autologous blood transfusions. JAMA 256:2378-2380, 1986. Blumberg N, Heal JM: Transfusion and recipient immune function. Arch Pathol Ldb Med 113:246-253, 1989.

Autologous Transfusions for Cancer Patients 5 . Alter HJ: You’ll wonder where the yellow went: A 15 year retrospective of post transfusion hepatitis. In Moore S B (ed): “Transfusion Transmitted Viral Disease.” Arlington, VA: American Association of Blood Banks, 1987, Ch 4, pp 53-86. 6. Rubin RH, Tolkoff-Rubin NE: Post transfusions viral infection. Transplant Proc 20:1112-1117, 1988.

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7. Stipp D: Number of auto-transfusions expected to rise due to AIDS panel endorsement. The Wall Street Journal, p 7, June 13, 1988. 8 . Holland PV, Schmidt PJ: “Standards for Blood Banks and Transfusion Services” (ed 12). Arlington, VA: American Association of Blood Banks, 1987.