Informed consent must be obtained prior to PRBC transfusion with a discussion of the risks, benefits and treatment alternatives to transfusion therapy. PRBCs are often stored in adsol (adenine saline, AS) secondary to a longer storage life (42 days) with a resultant hematocrit of 55–60 % due to the addition of 100 mL of AS per unit blood. All pediatric oncology patients should receive leukoreduced, irradiated PRBCs. Leukocytes are implicated as contributory to the majority of transfusion reactions; leukoreduction has been shown to significantly reduce febrile nonhemolytic transfusion reactions (FNHTRs) as well as infection with viral, bacterial, and protozoal pathogens, and specifically CMV transmission (van Marwijk Kooy et al. 1991; Chu 1999; Vamvakas and Blajchman 2001; Dzik 2002; Heddle 2004; King et al. 2004; Paglino et al. 2004; Yazer et al. 2004; Blumberg et al. 2005). Although leukoreduction decreases CMV transmission, CMV-seronegative units are thought safer in at-risk populations; specifically for pediatric oncology, consensus guidelines recommend CMV-seronegative units in patients receiving hematopoietic stem cell transplantation (HSCT) although this recommendation is controversial (Hillyer et al. 1994; Blajchman et al. 2001; Nichols et al. 2003; Gibson et al. 2004; Ljungman 2004; Vamvakas 2005). Additional studies have shown no difference in CMV transmission rates in HSCT patients receiving leukoreduced versus CMV-seronegative PRBCs (Bowden et al. 1995; Thiele et al. 2011; Nash et al. 2012). PRBC irradiation is recommended in all immunocompromised patients to prevent transfusion-associated graft-versus-host disease (TA-GVHD) by inactivating donor T-cell replication and engraftment in the host (Anderson et al. 1991; Moroff and Luban 1992; Dwyre and Holland 2008; Rühl et al. 2009). Similar to HSCT-related GVHD, TA-GVHD can present with fever, anorexia, vomiting, diarrhea, skin rash, as well as pancytopenia and hepatic dysfunction. Directed donation of PRBCs from family members is generally not recommended due to the cost and time required in addition to not being shown more safe in the prevention of transfusion-associated infection (Strauss et al. 1990).

Determination of the goal hgb should direct the volume of PRBCs transfused and is dependent on the patient’s clinical status, potential for ongoing blood loss and time to recovery from myelosuppressive chemotherapy. Generally 10–20 mL/kg of PRBCs are transfused, rounding to the nearest unit to avoid blood product wastage and historically given over 4 h although this practice is not well studied in hemodynamically stable children. In the patient without ongoing blood loss or alloimmunization, the expected rise in hgb is dependent on the hematocrit concentration of the PRBC product; for an AS preserved unit, the hgb is expected to increase by approximately 2 g/dL for each 10 mL/kg of PRBCs transfused (Davies et al. 2007). Anecdotal teaching that repeat hgb measurement must wait a certain period of time for reequilibration is poorly studied and likely unnecessary (Glatstein et al. 2005; Davies et al. 2007). Patients with severe chronic anemia (i.e., hgb <5 g/dL) are potentially at risk for transfusion-associated circulatory overload (TACO) due to the theoretical concern for cardiogenic pulmonary edema with transfusion in the patient with existing compensatory increase in plasma blood volume to near-normal levels. Variable practice exists, including slow transfusion of 5 mL/kg over 4 h, sometimes with the addition of a diuretic agent such as furosemide. Limited evidence suggests more liberal transfusion rates such as 2 mL/kg/h can be safely used in those patients without underlying evidence of hemodynamic instability or cardiopulmonary compromise (Jayabose et al. 1993; Agrawal et al. 2012).

Thrombocytopenia is a common side effect of intensive pediatric oncology therapy with potential risks for morbidity, dependent on the rate of platelet drop and seen more commonly when the platelet count is <20 × 10⁹/L (Belt et al. 1978; Rintels et al. 1994). Petechiae, spontaneous hemorrhage and mucosal bleeding are common with platelet count <20 × 10⁹/L while the risk for severe spontaneous or life-threatening hemorrhage is rare (Slichter and Harker 1978; Consensus Conference 1987; Gmür et al. 1991; Contreras 1998; Norfolk et al. 1998; Schiffer et al. 2001; Athale and Chan 2007). Thrombocytopenia occurs most commonly secondary to suppressed thrombopoiesis from chemotherapy, radiation therapy or infection. Thrombocytopenia at diagnosis in leukemia patients can be secondary to marrow infiltration as well as splenic sequestration in those with splenomegaly. Increased platelet consumption can occur due to hemorrhage and sepsis with secondary disseminated intravascular coagulation (DIC). Frequent platelet transfusion increases the risk of developing platelet antibodies and subsequent refractoriness to further transfusion; therefore, as with PRBC transfusion, the risks and benefits of platelet transfusion must be considered in each individual case prior to the decision to transfuse.

Patients with prolonged neutropenia are at increasing risk of infection and secondarily lack neutrophils to eradicate infection. Therefore it has been theorized that frequent granulocyte transfusion may be an effective method to fight serious infection in the severely neutropenic patient without imminent count recovery. Although theoretically promising and potentially shown beneficial in small observational studies, consistent data are lacking and some meta-analyses have failed to show a significant benefit (Vamvakas and Pineda 1997; Bishton and Chopra 2004; Robinson and Marks 2004; Grigull et al. 2006; Sachs et al. 2006; van de Wetering et al. 2007; Seidel et al. 2008; Massey et al. 2009; Peters 2009).

In the patient with severe, refractory or progressive bacterial or fungal infection and severe neutropenia likely to continue >1 week, granulocyte transfusion can be considered (Bishton and Chopra 2004). Donors should be mobilized with G-CSF and dexamethasone with a goal transfusion dose of >1.0 × 10⁹ cells/kg in the pediatric patient transfused daily for a minimum of 4–7 days (Chanock and Gorlin 1996; Klein et al. 1996; Massey et al. 2009). Granulocyte transfusion should be ABO compatible and crossmatched as well as irradiated to prevent TA-GVHD (Bishton and Chopra 2004). CMV-seronegative products should be used in CMV-seronegative patients to prevent CMV transmission (Bishton and Chopra 2004).

In the past, clerical error leading to ABO-incompatible blood transfusion and secondary acute hemolysis, as well as infectious complications, were the most common transfusion reactions (Williamson et al. 1999; Linden et al. 2000; Myhre and McRuer 2000; Stainsby et al. 2006). Now, due to improved blood safety, transfusion-related acute lung injury (TRALI) has become most common in the adult literature due to increased recognition, and generally noninfectious causes are much more common (Bolton-Maggs and Murphy 2004; Stainsby et al. 2006). Reactions to transfusion may range from mild to life-threatening and the clinician must be able to promptly recognize the potential severe reaction in the face of common transfusion-related symptoms such as fever. Acute reactions are defined as occurring within 24 h while delayed reactions occur beyond the acute period. Potential reactions include acute and delayed hemolysis, FNHTR, allergic reactions, TRALI, TACO, TA-GVHD and infectious complications. In the chronically transfused, alloimmunization to PRBC transfusion must be considered in addition to iron overload. Management of transfusion reactions is generally based on best practice and consensus guidelines rather than an evidence basis (Table 2.3).