Page 1968 - Hematology_ Basic Principles and Practice ( PDFDrive )

1742 Part XI Transfusion Medicine

with severe forms of PMN dysfunction are relatively rare, and no ran- Recipients were given 7.5 µg/kg G-CSF every 12 hours until blood
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domized clinical trials have been reported to establish the efficacy of PMNs were greater than or equal to 1.5 × 10 /L. Recipient blood
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therapeutic GTX in their management. Firm recommendations about PMNs were maintained at greater than 1.5 × 10 /L throughout the
the use of GTX to treat patients cannot be made. However, several 5 days of posttransplant GTX. By comparison, a historical group of
patients with chronic granulomatous disease, complicated by progres- control recipients treated with G-CSF, but no GTX, exhibited lower
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sive life-threatening fungal infections, have been reported to benefit. mean blood PMN counts of less than 0.5 × 10 /L posttransplant.
Because of the possibility of alloimmunization to leukocyte and red Prophylactic GTX seemed promising in this setting and perhaps
blood cell antigens plus the other risks of allogeneic transfusions, would have been even more effective (i.e., higher recipient blood
such as pulmonary reactions and transfusion-transmitted infections, PMN counts and fewer infections) if given daily.
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therapeutic GTX are recommended only for progressive infections In another study, Adkins et al transfused 23 autologous periph-
that cannot be controlled with antimicrobial drugs. Because of lifelong eral HPC recipients with PMNs collected from first-degree relative
problems with infections, prophylactic GTX are impractical. donors (see Table 114.6). Leukapheresis was performed on post-
Neonates (infants within the first month of life) are another group transplant days 2, 4, 6, and 8, and GTX were infused. Recipients
of patients who may suffer life-threatening bacterial infections caused, were given 5 µg/kg G-CSF daily until the blood PMN count was
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at least in part, by PMN dysfunction and neutropenia—absolute or greater than or equal to 1.5 × 10 /L. Recipients were studied for the
relative (i.e., normal neonates exhibit a physiologic neutrophilia effects of lymphocytotoxic antibodies (i.e., leukocyte alloimmuniza-
compared with normal PMN counts in older children and adults)— tion) on GTX effectiveness. The 15 recipients who did not exhibit
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consequently, absolute blood PMN counts as high as 3.0 × 10 /L lymphocytotoxic antibodies during the 10-day study period experi-
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might prompt consideration of GTX in neonates. Although four of enced a mean of 4.1 febrile days and required 7.3 days of antibiotics.
six controlled trials assessing the efficacy of therapeutic GTX in Values for the eight recipients with lymphocytotoxic antibodies were
neonatal sepsis found a significant benefit for GTX, this form of less desirable—6.3 febrile days and 10.5 days of antibiotics. Rates of
therapy is rarely used today. Accordingly, they will not be discussed documented infections were not reported.
further. No firm conclusions can be drawn from these reports of modern
prophylactic GTX because (1) no nontransfused control subjects
PROPHYLACTIC GRANULOCYTE TRANSFUSIONS IN were included, (2) few patients were studied, and (3) most patients
were given GTX every other day, rather than daily—possibly provid-
NEUTROPENIC PATIENTS ing a lower-than-optimal dose of PMNs. Modern prophylactic GTX
appear promising, but their efficacy, potential adverse effects, and
Based on historical reports, prophylactic GTX were of marginal economic analysis await definition by randomized clinical trials.
value. In 12 reports, benefits were few, whereas risks and expenses
were substantial. However, some measure of success was found in 7
of 12 studies; the remaining 5 studies failed to show a benefit for ALTERNATIVE OR ADDITIVE MEASURES TO
prophylactic GTX. In none of these 5 negative studies were large GRANULOCYTE TRANSFUSIONS
numbers of PMNs obtained from matched donors and transfused
daily. In a situation analogous to that for the negative therapeutic Patients with severe neutropenia, particularly those undergoing
GTX trials, the failure of prophylactic GTX might be explained, at intense chemotherapy or HPC transplantation, exhibit a variety of
least in part, by inadequate transfusions. abnormalities in multiple body defense mechanisms, most of which
The role of modern prophylactic GTX (i.e., from G-CSF–stimu- cannot be corrected by GTX. Consequently infections that occur in
lated donors) has not been established by definitive clinical trials. these patients often occur after the period of severe neutropenia and
However, two factors suggest possible success: (1) because of the accordingly do not respond to GTX. To bolster body defenses, a
rapid recovery from myeloablation, hastened by peripheral blood number of additional therapies have been evaluated, two of which
HPC transplantation plus treatment of patients with recombinant are the use of recombinant myeloid growth factors (i.e., cytokines)
growth factors such as G-CSF, the period of severe neutropenia and intravenous immunoglobulin (IVIg). A critical analysis of the
may be as short as 1 week; and (2) this relatively brief period of biology and clinical use of these agents is beyond the scope of this
severe neutropenia might literally be eliminated by transfusing large chapter.
doses of PMNs collected from donors stimulated with G-CSF plus
corticosteroids. A few studies have begun to explore this possibility
(Table 114.6). AUTHOR’S APPROACH TO THERAPEUTIC GTX
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Adkins et al transfused 10 allogeneic marrow recipients with
PMNs collected from their human leukocyte antigen (HLA)-matched 1. Consider for severe bacterial, yeast, or other fungal infection in a
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sibling marrow donors (see Table 114.6). Leukapheresis was per- neutropenic patient (<0.5 × 10 PMNs/µL blood) when the
formed on days 1, 3, and 5 posttransplant, and GTX were infused. infection progresses despite optimal antimicrobial therapy.

TABLE Modern Prophylactic Granulocyte Transfusion Studies Using Neutrophils Collected From Granulocyte Colony-Stimulating
114.6 Factor–Stimulated Donors in Hematopoietic Progenitor Cell Transplant Recipients
PMNs × 10
10
Investigator per Each GTX Stimulation Leukapheresis Outcomes
Adkins et al 24 4.1 (day 1) G-CSF 5 µg/kg × 5 Hetastarch 60% (6 of 10) afebrile
5.1 (day 3) Days posttransplant 7 L processed 40% (4 of 10) febrile
6.1 (day 5) Days 1, 3, and 5 3 culture positive
Adkins et al 25 5.6 (day 2) G-CSF 10 µg/kg Hetastarch Reduction of fever and antibiotics if no leukocyte antibodies
7.0 (day 4) 7 L processed
8.5 (day 6) Days 2, 4, 6, and 8
9.9 (day 8)
G-CSF, Granulocyte colony-stimulating factor; GTX, granulocyte transfusions; PMN, neutrophil.