Page 1716 - Hematology_ Basic Principles and Practice ( PDFDrive )

1526 Part IX Cell-Based Therapies

donors (n = 964) and 7% of male donors (n = 1444) on the first day prevent collapse during aspiration of blood, as well as a tip design
of apheresis, falling to 10% and 4%, respectively, on the second day that decreases local recirculation of blood and the resulting decrease
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of collection (if performed). Most (51%) of reported adverse events in apheresis efficiency. Catheters of 10 F or larger size are appropriate
were related to citrate infusion. A smaller proportion of donors (22%) for adult patients. Pediatric patients, whose blood flow rates are
reported problems with venous access. Rare (1–6% of events) adverse considerably slower, may use catheter sizes of 5–7 F. 105
events included hypertension or hypotension, allergic reactions,
fatigue, and syncope. The placement of a central venous catheter was
required by 17% of female donors and 4% of male donors. Also, Anticoagulation for PBSC Collection
larger-volume and repetitive exchanges will result in platelet deple-
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tion. The platelet count may reach its nadir several days after comple- Anticoagulants are added to the blood during apheresis to prevent
tion of the apheresis collections and discontinuation of G-CSF, and clotting of the extracorporeal circuit and clumping of cells in the
donors should be counseled in this regard. component. Citrate anticoagulants have a proven record of safety in
Important caveats are that the donors in this analysis from the the apheresis of healthy platelet donors. The major drawback is the
unrelated donor registry met strictly defined health criteria and were risk for a symptomatic decrease in the level of ionized calcium
between 18 and 69 years of age. A higher probability of adverse events (“citrate toxicity”), especially during processing of large volumes of
may be expected in patients and in donors of older (or younger) blood. Citrate ions chelate calcium ions (and other divalent cations
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age. For example, in an older retrospective publication, Goldberg such as magnesium), making them unavailable for Ca -dependent
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and colleagues studied the complications occurring during 554 metabolic reactions. ACD-A contains 10.67 g of citrate per 500-mL
PBSC collections from 75 consecutive patients. Patient diagnoses volume in the form of trisodium citrate and citric acid. Citrate is
and the mobilization treatment regimens were varied. All but one diffused throughout the extravascular space, and this diffusion is the
patient had subclavian or jugular venous system catheters placed for first defense against citrate toxicity. The body size and difference in
apheresis. A median of nine collections per patient were performed muscle mass between men and women results in an increased risk for
using a discontinuous-flow apheresis device. The most common citrate toxicity for women in particular and smaller donors in general.
problems were related to the venous catheters: 50% of patients Metabolism by liver, kidney, and muscle also reduces the concentra-
developed at least one occlusion. Hypocalcemia occurred in 14.6% tion of citrate. Metabolism of citrate becomes an important clinical
of patients and hypotension in 13.3%. Sixteen percent of patients consideration during processing of larger blood volumes or at higher
experienced infectious complications during the PBSC collection rates of blood flow. The initial signs of citrate toxicity include cir-
period. cumoral or acral paresthesias and may progress to nausea, vomiting,
Staffing of the apheresis unit should be appropriate for the medical loss of consciousness, tetany, and seizures. Because pediatric patients
condition of the patients undergoing apheresis. Staffing must include may not be able to relate the initial symptoms of the condition, citrate
nurses familiar with the care of the oncologic patient who may be toxicity should be considered as the cause of any change of behavior,
recovering from marrow hypoplasia complicated by neutropenic fever such as crying, during the apheresis procedure. Citrate toxicity is
requiring multiple medications and the care of a central venous prevented by limiting the quantity of citrate infused either by decreas-
catheter. Collection of PBSCs by apheresis in the outpatient setting ing the blood flow rate through the apheresis device or changing the
should be performed only after careful review of the medical support blood-to-citrate ratio. The processing of blood from patients experi-
requirements for the individual patient or donor, and it should never encing the initial symptoms of citrate toxicity should be temporarily
be assumed to be a safer alternative for the donor or patient with a halted until the symptoms abate and then resumed at a slower rate.
serious comorbid illness than marrow harvesting conducted in the The benefit of oral calcium supplements for these patients is not
intensive care setting of the operating room. proven and may cause abdominal discomfort. Heparin can be used
as a replacement for some or all of the citrate, although additional
citrate should be added to the component bag to prevent clumping
Venous Access of platelets. Some centers that use citrate anticoagulants also admin-
ister intermittent or continuous infusions of calcium gluconate
Adequate venous access is required for optimal apheresis technique. during the procedure, especially if large volumes of blood are being
Continuous-flow apheresis devices require two-lumen access with a processed. However, excessive calcium replacement can induce cardiac
stable blood flow capacity generally greater than 20 mL/min. Single- dysfunction.
lumen access may be used with discontinuous-flow apheresis devices,
although at a much slower rate of blood processing. The great major-
ity (≈95%) of adult male allogeneic PBSC donors have adequate arm Large-Volume Leukapheresis
veins for the procedure to be conducted “vein to vein,” with female
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donors more likely to require alternate venous access. Some donors, The apheresis device has a uniform and fairly reproducible efficiency
especially those with small veins and undergoing several daily proce- of collection. Thus, for a consistent quantity of blood processed
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dures, may require placement of a temporary venous catheter. Venous through the machine, the quantity of CD34 cells collected is directly
access for the patient undergoing collection for autologous PBSC related to the number present in the peripheral blood. Greater quanti-
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transplantation is much more heterogeneous. Vein-to-vein procedures ties of CD34 cells can be collected by increasing the number of these
can be performed, even on several consecutive days, with proper cells in the peripheral circulation or by increasing the volume of blood
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phlebotomy technique and postcollection care of the phlebotomy processed in each procedure (LVL). For patients with lower CD34
site. Most patients received previous chemotherapy or are proceeding cell levels, multiple apheresis procedures will be required to achieve
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directly to transplantation, conditions for which tunneled access is the target dose of CD34 cells needed for transplantation. An alter-
commonly placed. Ideally, this venous access should be appropriate nate approach is to process the same total quantity of blood but in
both for the apheresis procedures and the subsequent transplant. fewer, longer procedures. LVL is not standardly defined, but in
Length, lumen size, and wall stiffness all affect the blood flow that general usage it refers to processing of more than two or three times
can be achieved through a catheter. For this reason, the commonly the patient’s blood volume. Typically, the quantity of blood processed
used dual-lumen Hickman or Broviac catheters are usually unsuitable is six or more times the patient’s blood volume, often 25–36 L of
for apheresis, as are all subcutaneously placed ports. Most triple- blood. The advantage of LVL is that it reduces the number of days
lumen catheters are inadequate because of the small lumen size. If of cytokine administration and apheresis, with associated reduced
such access is already in place, consideration can be given to replace- costs of laboratory processing and testing. The apheresis techniques
ment with a shorter, stiffer tunneled catheter or to placement of a are the same as those used for processing of smaller volumes of blood,
temporary percutaneous dialysis/apheresis catheter. The catheters although blood flow rates may be increased to reduce the time
designed for dialysis and apheresis have adequate wall thickness to required. The risks of LVL are the increased time required and the