Page 458 - Williams Hematology ( PDFDrive )

432 Part V: Therapeutic Principles Chapter 28: Therapeutic Apheresis: Indications, Efficacy, and Complications 433

ADVERSE EFFECTS OF RED CELL EXCHANGE effect. 107–113 Procedures in which 1.5 to 2.0 blood volumes are processed,
AND ERYTHROCYTAPHERESIS and crystalloid replacement fluids are used to manage fluid balance, can
108,112,113
lower the platelet count by 30 to 60 percent
; however, throm-
Red cell exchange conveys risks related to red cell transfusion including bocytapheresis without concomitant chemotherapy is ordinarily not
febrile, allergic and hemolytic transfusion reactions, acute lung injury, a practical means for controlling the platelet count beyond the acute
vasovagal reactions, and transfusion-transmitted disease. Hypocalce- setting. Weekly thrombocytapheresis, beginning in the fifth gestational
mic toxicity resulting from the use of citrate-based anticoagulants in the week, has been used in the management of a high-risk pregnant patient
apheresis circuit and in the red cell replacement units may also occur. with essential thrombocythemia. Thrombocytapheresis has been
113
Erythrocytapheresis conveys similar risks but not the risks associated reported as effective acute therapy in the case of a patient with immune
with red cell transfusions. 48 thrombocytopenic purpura, treated with romiplostim, who developed
platelet counts as high as 2 × 10 /μL and acute neurologic symptoms in
6
114
THERAPEUTIC LEUKOCYTAPHERESIS the days following splenectomy, and can be used to prepare acutely
symptomatic patients with poorly controlled severe thrombocytosis for
ASFA has designated hyperleukocytosis (white blood cell count cardiovascular surgery. 115
>100,000/μL in acute myeloid leukemias [Chaps. 83 and 88], white cell
count >400,000/μL in acute lymphoblastic leukemia [Chap. 91] with EXTRACORPOREAL
leukostasis as a category I indication for therapeutic leukocytapher-
4
esis. Asymptomatic hyperleukocytosis is designated a category PHOTOCHEMOTHERAPY
III indication, reflecting limited and conflicting published evidence (PHOTOPHERESIS)
regarding the utility of leukocytapheresis as prophylaxis. Hyperleu-
4
kocytosis, which occurs in 5 to 13 percent of newly presenting cases Extracorporeal photochemotherapy (ECP) is a treatment process in
of adult acute myelogenous leukemia and 12 to 25 percent of pediatric which a patient’s mononuclear white blood cells are manipulated out-
acute myelogenous leukemia is a risk factor for early mortality, often side of the body such that their reinfusion into the patient results in
from leukostasis and pulmonary and/or central nervous system hem- down regulation of cytotoxic T-cell activity. This procedure involves
116
orrhage. 93–97 The processing of 1.5 to 2.0 blood volumes, using crys- collection of circulating mononuclear cells by centrifugal apheresis,
talloid or colloid fluids to maintain fluid balance, with or without a exposing them to 8-methyoxypsoralen (8-MOP, a photoactivating
sedimentation agent such as 6 percent hydroxyethyl starch to enhance agent) and then to ultraviolet A light (UVA), and then reinfusing the
separation of white cells from red cells, can reduce the circulating white treated cells into the patient. ECP was originally approved for Medi-
56
cell count by upward of 60 percent, but without a clear effect on the care reimbursement in 1998 for palliative treatment of skin manifesta-
4,98
rate of early mortality in patients with acute myeloid leukemia and tions of cutaneous T-cell lymphoma (Chap. 103) unresponsive to other
hyperleukocytosis with or without leukostasis. 99,100 In any case, leuko- therapy and was further found “reasonable and necessary” for treatment
cytapheresis is not undertaken without initiating measures to mitigate of acute cardiac allograft rejection and chronic graft-versus-host disease
the risk of tumor lysis syndrome, including intravenous hydration, (Chap. 23) unresponsive to standard treatments in 2006. It was devel-
117
lowering of plasma uric acid using allopurinol or urate oxidase, and, oped based on an earlier treatment called PUVA (psoralen plus ultravi-
if urate oxidase is not used, intravenous sodium bicarbonate to alka- olet A) in which a patient would take an oral dose of 8-MOP and then
101
linize the urine. Leukapheresis would ordinarily not be considered stand in a UVA light box thus exposing affected skin to treatment. With
primary therapy in patients who present with high blast counts but ECP, only the white cells collected by apheresis are exposed to 8-MOP
without symptoms of leukostasis 4,100 and UVA, thus only approximately 0.25 percent of the oral dose equiv-
alent of 8-MOP is used. The precise mechanism of action of ECP is
116
still under investigation, but likely involves a process of immunomod-
THERAPEUTIC ulation. UVA-activated 8-MOP intercalates within nuclear DNA of
118
THROMBOCYTAPHERESIS normal and malignant T lymphocytes and causes the treated T cells,
but not treated monocytes, to undergo apoptosis by 24 hours after treat-
Thrombocytapheresis refers to the selective removal of platelets from a ment. 119,120 Immunologic consequences of phagocytosis of reinfused
patient, for therapeutic purposes using a blood processing (apheresis) apoptotic cells include induction of major histocompatibility complex
device. ASFA lists symptomatic thrombocytosis in patients with mye- (MHC) class I–restricted CD8+ cytotoxic T lymphocytes through the anti-
loproliferative neoplasms (Chaps. 83 and 85) as a category II indica- gen-presenting activity of human dendritic cells and the elaboration by
tion for thrombocytapheresis. Thrombocytapheresis for prophylaxis monocytes and macrophages of immunosuppressive cytokines includ-
4
121
in asymptomatic patients or to lower the platelet count in cases of ing interleukin (IL)-10 and IL-1 receptor antagonist. Furthermore,
secondary or reactive thrombocytosis is listed as a category III (see ECP results in an increase in CD83+, CD86+ plasmacytoid (DC2) den-
102
Table 28–1) indication because the available data do not firmly estab- dritic cells with a concordant diminution in CD80+, CD123+ mono-
lish a role for thrombocytapheresis in these circumstances and decision cytoid (DC1) dendritic cells. The DC2 cells stimulate T-helper type 2
making should be highly individualized. Secondary thrombocytosis (Th2) cells to secrete inhibitory cytokines (e.g., IL-4, IL-10, IL-13) while
per se does not convey a risk of thromboembolic morbidity absent inhibiting stimulation of T-helper type 1 (Th1) cells that secrete proin-
confounding factors such as malignancy or major surgery. 103–105 Rapid flammatory cytokines (e.g., IL-2, interferon-γ) and thus inhibiting Th1-
lowering of an elevated platelet count, using apheresis and/or chemo- mediated alloreactivity. ECP also appears to result in an increase in a
122
therapy, is indicated for patients with myeloproliferative neoplasms who population of circulating CD4+, CD25+, CD69− CTLA-4+ regulatory
present with clinical syndromes of thrombocytosis with microvascular T cells (T REG ) that are immunosuppressive and are involved in trans-
106
thrombosis such as digital or cerebral ischemia. Several case series plant tolerance. Such induced immunologic responses to ECP are pre-
123
and case reports have reported successful, rapid lowering of the plate- sumed to explain observed clinical benefit in diverse conditions such
let count in symptomatic patients in whom chemotherapy was either as cutaneous T-cell lymphoma, chronic graft-versus-host disease, and
not an immediate option or was judged to have an insufficiently rapid cardiac transplant rejection. 124–126

Kaushansky_chapter 28_p0427-0436.indd 433 9/17/15 6:05 PM