Page 1965 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 114 Principles of Neutrophil (Granulocyte) Transfusions 1739

Infectious Problems in Neutropenic Patients Treated Results of Seven Controlled Studies Evaluating
TABLE With Historical Granulocyte Transfusions in 34 TABLE Historical Therapeutic Granulocyte Transfusions in
114.1 Studies 114.2 Neutropenic Patients

Type of Infection Treated Evaluable Success Rate (%) Study Group Control Group
Bacterial septicemia 298 206 127/206 (62) Investigators Success n Survival (%) n Survival (%)
Sepsis organism 132 39 18/39 (46) Higby et al 5 Yes 17 76 19 26
unspecified 6
Vogler and Winton Yes 17 59 13 15
Invasive yeast or other 83 77 28/77 (36) Herzig et al 4 Yes 13 75 14 36
fungus
Alavi et al 1 Partial 12 82 19 62
Pneumonia 120 11 7/11 (64)
Graw et al 3 Partial 39 46 37 30
Localized infections 143 47 39/47 (83)
Winston et al 7 No 48 63 47 72
Fever etiology unknown 184 85 64/85 (75)
Fortuny et al 2 No 17 78 22 80

TABLE Design of Seven Controlled Studies Evaluating Historical Therapeutic Granulocyte Transfusions in Neutropenic Patients
114.3
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Investigators Randomized? Collection Method Dose (× 10 ) Schedule HLA a WBC a
Higby et al 5 Yes Filtration 2.2 Daily No Yes
Vogler and Winton 6 Yes Centrifugation 2.7 Daily Yes Yes
Herzig et al 4 Yes Filtration 1.7 Daily No Yes
Centrifugation 0.4 Daily No Yes
Alavi et al 1 Yes Filtration 5.9 Daily No No
Graw et al 3 No Filtration 2.0 Daily No Yes
Centrifugation 0.6 Daily No Yes
Winston et al 7 Yes Centrifugation 0.5 Daily No No
Fortuny et al 2 No Centrifugation 0.4 Daily No Yes
a Donors selected to be compatible with recipient either by HLA typing (A and B loci matched, at least in part) or by leukocyte crossmatching.
HLA, Human leukocyte antigen; WBC, white blood cell.

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leukapheresis, 2,3,7 the dose was extremely low (0.41 to 0.56 × 10 per graft is T-lymphocyte depleted to diminish graft-versus-host disease.
concentrate). As another factor, investigators in two of the four nega- Hence all types of infection pose a threat, with yeast and other fungal
1,7
tive studies made no provision for the possibility of leukocyte infections being major problems. In a series of 1186 marrow trans-
alloimmunization, because donors were selected solely on the basis plant patients, 10% developed a noncandidal fungal infection, with
of erythrocyte compatibility. Finally, control subjects responded only 17% of infected patients surviving. When the marrow graft is
reasonably well to antibiotics alone in three of the four negative depleted of T lymphocytes, the rate of infection is increased twofold
studies, 1,3,7 suggesting that some patients fared so well with conven- to sevenfold above that occurring with standard bone marrow
tional treatment that they had no apparent need for additional thera- transplantation.
peutic modalities. Data are insufficient to determine the proper role of GTX in
These impressions from the seven controlled GTX trials have been treating yeast or other fungal infections (which are the most difficult
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analyzed by formal meta-analysis, with conclusions that the dose of to treat). Historical case reports, experimental studies in animals, and
PMNs transfused and the survival rate of the nontransfused control experience in treating patients with chronic granulomatous disease
subjects were primarily responsible for the differing success rates of have supported the efficacy of GTX in fungal infections. In contrast,
the historical studies. In clinical settings in which the survival rate of a large historical clinical study reported that GTX collected without
nontransfused control subjects was low, study subjects benefited from G-CSF donor stimulation were of no benefit in treating yeast or other
receiving adequate doses of GTX, prompting the authors to suggest fungal infections in 87 bone marrow transplant patients, 50 of whom
that severely neutropenic patients with life-threatening infections received GTX. Although this study was a retrospective review with
should be considered to receive GTX given in adequate doses. 8 several shortcomings, it is supported by the disappointing finding of
the poor response of invasive/tissue fungal infections in neutropenic
THERAPEUTIC GTX FOR NEUTROPENIC INFECTIONS: patients to even modern GTX in some reports.
At this time, two randomized clinical trials of therapeutic GTX
MODERN EXPERIENCE collected after G-CSF donor stimulation have been reported, but fail
to clearly establish the efficacy or potential toxicity of modern GTX.
Bacterial, yeast, and other fungal infections occur frequently in Their shortcomings will be discussed. Because the randomized trials
patients with severe neutropenia or PMN dysfunction, and when fail to provide definitive information, five case reports (Table 114.4)
these infections fail to promptly respond to antimicrobial drugs, they and six uncontrolled studies of multiple patients (Table 114.5) will
pose a major challenge for which modern therapeutic GTX offer a be reviewed to provide as much information as possible for making
possible answer. Recipients of HPC transplants—particularly marrow clinical decisions. 9–19
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transplant patients—often become severely neutropenic and exhibit Clarke et al and Catalano et al each reported single patients (see
PMN dysfunction shortly after transplant. Importantly, they manifest Table 114.4) with aplastic anemia undergoing HPC transplantation
defective cellular and humoral immunity for months after transplan- and with fungal infections that responded favorably to strikingly
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tation. Altered immunity is particularly profound when the HPC different doses of PMNs. Similarly, Ozsahin et al and Bielorai et