Hydroxyethyl Starch and Prednisone as Adjuncts to Granulocyte Collection J. D. BEARDENJII, C. A. COLTMAN, JR.,
AND
G. A. RATKIN
From the Wilford Hall USAFMedical Center. Lackland AFB. Texas
A total of 232 leukaphereses were performed with a continuous flow (CFC) of 89 donors related to recipients to obtain granulocytes for infected granulocytopenic recipients. One hundred fifteen runs were done without pretreatment of the donors and were used as controls. Pharmacological pretreatment of. the remaining one hundred seventeen donors included Prednisone, given in an oral dose (50 mg) the evening prior to the run, and/or 250ml of 6 per cent hydroxyethyl starch added to the input line of the CFC throughout the run. A median of 9.2 liters of donor blood was processed with each run. The pretreatment of the donors with Prednisone plus the addition of HES to the input line significantly increased the number of granulocytes collected. Donors tolerated the leukapheresis procedure well, and no significant side effects were associated with Prednisone or H E S administration. Early and frequent use of such granulocytes was effective in the short-term control of fever in the granulocytopenic recipients who failed to respond to 48 hours of broad spectrum antibiotic coverage.
Materials and Methods
leukapheresis on 89 donors related to t h e recipients for the treatment of 63 episodes of antibiotic resistant infection in 58 granulocytopenic patients. An American Instrument Company continuous flow cell separator (celltrifuge) was employed for leukapheresis as previously d e s ~ r i b e d . ~The . ~ . ~median blood flow rate was 50 ml/minute; the median duration of the run was 3.1 hours and median volume of blood processed was 9.2 per run. T e s t s for H L A histocompatibility were performed and the most closely matched related donor was chosen in every instance. Donors were HBsAg negative and were ABO compatible with the recipients. All donors and recipients gave their informed cons en t . Citrat e- phosphat e-dex trose (150-200 ml) anticoagulant was used during the run. One hundred fifteen runs were performed without donor manipulation and will be referred to as controls. Twenty-seven runs were performed with the infusion of 250 ml of 6% hydroxyethyl starch (HES) into the input line of the Celltrifuge. Twenty-six runs were performed without hydroxyethyl starch, but the the pretreatment of the donor with 50 mg of oral Prednisone the evening prior to the run. Finally, 64 runs were performed with both hydroxyethyl starch and pretreatment of the donor with 50 mg of Prednisone. Granulocytes harvested were used in the treatment of patients with acute leukemia aplastic anemia or lymphoma. At the time of infusion the patients were granulocytopenic (less than 500/ml), had fever greater than 38.3 C, that had not responded to treatment with Carbenicdlin and Gentamicin for 48 hours. T h e patients with leukemia had hypocellular marrows secondary to chemotherapy. Many patients had received additional antibiotics and Arnphotericin B was used for suspected or proven mycotic infections.
During the first 18 months of leukapheresis by continuous flow centrifugation we performed 232
Results
Received for publication January 15, 1976; accepted May 10, 1976.
A cumulative distribution was used to express the results of the total leukocyte collection (Fig. 1) and the total granulocyte collection (Fig. 2) of all
BACTERIAL and fungal infections, refractory to a n t i b i o t i c t h e r a p y , a r e major contributors of t h e morbidity and mortality of patients with acute leukemia and severe g r a n u l o c y t o p e n i a . T h e successful use of g r a n u l o c y t e t r a n s f u s i o n o b t a i n e d by continuous flow centrifugation and by filtra~ study tion h a v e been d e ~ c r i b e d . ~ . ' . 'This deals with our experience with leukapheresis b y c o n t i n u o u s flow c e n t r i f u g a t i o n . T h e effects o f p h a r m a c o l o g i c m a n i p u l a t i o n to improve granulocyte yields are presented and t h e overall effectiveness o f the transfusions is analyzed in terms of febrile response and survival.
141 Cranslusion Mar.-Apr. 1977
Volume 17 Number 2
142
Transfusion
BEARDEN ET AL.
Mar.-Apr. 1917
0 0 4
0 L
b
FIG. I . Total leukocytes (WBC) per liter of whole blood processed from the donors expressed as a cumulative proportion.
TOTL
115 0 CONTROL
0.0
1.0
3.0
2.0
4.0
5.0
BES ONLY
27
A
26
a PREDNISONE OULY
84
*
PREDRISDNE + HES
8.0
7.0
8.0
WBC/L BLOOD (=log) NORMAL DONORS
t h e leukaphereses performed. Results a r e expressed as the total number of leukocytes collected times 10Q/literof whole blood processed. The median number of total leukocytes and granulocytes are shown in Table 1. The four donor groups were compared utilizing a 2-tailed Wilcoxon test (Table 2). There were no Table 1. Yield of Total Leukocytes and Granulocytes Expressed as Total Number Collected Times lOg/Liter of Whole Blood Processed
N Leukocytes Controls HES alone Prednisone alone HES + Prednisone Granulocytes Controls HES alone Prednisone alone HES + Prednisone
Median
Range
115 27 26 64
1.785 1.965 1.490 2.630
0.11 -9.90 0.11 -4.45 0.45 -5.40 0,769-5.50
115 27
0.61 15 0.6285
26
0.7830
64
1.560
0.01 -4.76 0.18 -3.03 0.14 -2.42 0.13 -4.94
significant differences in numbers of leukocytes collected from control donors and those receiving HES or Prednisone alone. Those 64 donors receiving Prednisone + HES produced significantly higher leukocyte yields than were obtained in the other three groups of donors (P
AND
G. A. RATKIN
From the Wilford Hall USAFMedical Center. Lackland AFB. Texas
A total of 232 leukaphereses were performed with a continuous flow (CFC) of 89 donors related to recipients to obtain granulocytes for infected granulocytopenic recipients. One hundred fifteen runs were done without pretreatment of the donors and were used as controls. Pharmacological pretreatment of. the remaining one hundred seventeen donors included Prednisone, given in an oral dose (50 mg) the evening prior to the run, and/or 250ml of 6 per cent hydroxyethyl starch added to the input line of the CFC throughout the run. A median of 9.2 liters of donor blood was processed with each run. The pretreatment of the donors with Prednisone plus the addition of HES to the input line significantly increased the number of granulocytes collected. Donors tolerated the leukapheresis procedure well, and no significant side effects were associated with Prednisone or H E S administration. Early and frequent use of such granulocytes was effective in the short-term control of fever in the granulocytopenic recipients who failed to respond to 48 hours of broad spectrum antibiotic coverage.
Materials and Methods
leukapheresis on 89 donors related to t h e recipients for the treatment of 63 episodes of antibiotic resistant infection in 58 granulocytopenic patients. An American Instrument Company continuous flow cell separator (celltrifuge) was employed for leukapheresis as previously d e s ~ r i b e d . ~The . ~ . ~median blood flow rate was 50 ml/minute; the median duration of the run was 3.1 hours and median volume of blood processed was 9.2 per run. T e s t s for H L A histocompatibility were performed and the most closely matched related donor was chosen in every instance. Donors were HBsAg negative and were ABO compatible with the recipients. All donors and recipients gave their informed cons en t . Citrat e- phosphat e-dex trose (150-200 ml) anticoagulant was used during the run. One hundred fifteen runs were performed without donor manipulation and will be referred to as controls. Twenty-seven runs were performed with the infusion of 250 ml of 6% hydroxyethyl starch (HES) into the input line of the Celltrifuge. Twenty-six runs were performed without hydroxyethyl starch, but the the pretreatment of the donor with 50 mg of oral Prednisone the evening prior to the run. Finally, 64 runs were performed with both hydroxyethyl starch and pretreatment of the donor with 50 mg of Prednisone. Granulocytes harvested were used in the treatment of patients with acute leukemia aplastic anemia or lymphoma. At the time of infusion the patients were granulocytopenic (less than 500/ml), had fever greater than 38.3 C, that had not responded to treatment with Carbenicdlin and Gentamicin for 48 hours. T h e patients with leukemia had hypocellular marrows secondary to chemotherapy. Many patients had received additional antibiotics and Arnphotericin B was used for suspected or proven mycotic infections.
During the first 18 months of leukapheresis by continuous flow centrifugation we performed 232
Results
Received for publication January 15, 1976; accepted May 10, 1976.
A cumulative distribution was used to express the results of the total leukocyte collection (Fig. 1) and the total granulocyte collection (Fig. 2) of all
BACTERIAL and fungal infections, refractory to a n t i b i o t i c t h e r a p y , a r e major contributors of t h e morbidity and mortality of patients with acute leukemia and severe g r a n u l o c y t o p e n i a . T h e successful use of g r a n u l o c y t e t r a n s f u s i o n o b t a i n e d by continuous flow centrifugation and by filtra~ study tion h a v e been d e ~ c r i b e d . ~ . ' . 'This deals with our experience with leukapheresis b y c o n t i n u o u s flow c e n t r i f u g a t i o n . T h e effects o f p h a r m a c o l o g i c m a n i p u l a t i o n to improve granulocyte yields are presented and t h e overall effectiveness o f the transfusions is analyzed in terms of febrile response and survival.
141 Cranslusion Mar.-Apr. 1977
Volume 17 Number 2
142
Transfusion
BEARDEN ET AL.
Mar.-Apr. 1917
0 0 4
0 L
b
FIG. I . Total leukocytes (WBC) per liter of whole blood processed from the donors expressed as a cumulative proportion.
TOTL
115 0 CONTROL
0.0
1.0
3.0
2.0
4.0
5.0
BES ONLY
27
A
26
a PREDNISONE OULY
84
*
PREDRISDNE + HES
8.0
7.0
8.0
WBC/L BLOOD (=log) NORMAL DONORS
t h e leukaphereses performed. Results a r e expressed as the total number of leukocytes collected times 10Q/literof whole blood processed. The median number of total leukocytes and granulocytes are shown in Table 1. The four donor groups were compared utilizing a 2-tailed Wilcoxon test (Table 2). There were no Table 1. Yield of Total Leukocytes and Granulocytes Expressed as Total Number Collected Times lOg/Liter of Whole Blood Processed
N Leukocytes Controls HES alone Prednisone alone HES + Prednisone Granulocytes Controls HES alone Prednisone alone HES + Prednisone
Median
Range
115 27 26 64
1.785 1.965 1.490 2.630
0.11 -9.90 0.11 -4.45 0.45 -5.40 0,769-5.50
115 27
0.61 15 0.6285
26
0.7830
64
1.560
0.01 -4.76 0.18 -3.03 0.14 -2.42 0.13 -4.94
significant differences in numbers of leukocytes collected from control donors and those receiving HES or Prednisone alone. Those 64 donors receiving Prednisone + HES produced significantly higher leukocyte yields than were obtained in the other three groups of donors (P
