Management of Tumor Supportive Care in Pediatric Oncology irantextbook.ir 93df

alkalinization due to potential risk of calcium phosphate precipitation are not recommended Coiffi er et al. 2008 ; Tosi et al. 2008 ; Howard et al. 2011 ; Vaitkevičienė et al. 2013 . Rasburicase is contraindicated in patients with glucose- 6-phosphate dehydrogenase G6PD defi ciency and methemoglobinemia Tosi et al. 2008 ; Cairo et al. 2010 ; Howard et al. 2011 ; Vaitkevičienė et al. 2013 .

6.7 Leukapheresis

The most recent recommendations by the American Society for Apheresis ASFA suggest leukapheresis as fi rst-line therapy for patients with leukostasis secondary to HL due to the potential to impact early death, although long- term outcome is unaffected Schwartz et al. 2013 . However, the potential to impact early death through leukapheresis was not shown in a meta-analysis of AML studies by Oberoi et al. 2014 . The role of apheresis as leukostasis pro- phylaxis with HL is not established but may be considered Schwartz et al. 2013 . Per the ASFA guidelines, the utilization of leukapheresis is listed as a strong recommendation with moder- ate-quality evidence for treatment of leukostasis symptoms and should be considered as a weak recommendation for leukostasis prophylaxis in higher-risk AML patients e.g., M4M5 sub- types, rapidly rising blast count with WBC 100 × 10 9 L and ALL patients with WBC 400 × 10 9 L Schwartz et al. 2013 . Per the ASFA guidelines, leukapheresis should not be utilized solely for the prevention or treatment of TLS in patients with HL Schwartz et al. 2013 . These recommendations are unchanged from the previous 2007 and 2010 ASFA guidelines Szczepiorkowski et al. 2007 , 2010 . No specifi c contraindication to the use of leukapheresis in APL patients is included in these guidelines although it is mentioned as a relative contraindi- cation in other guidelines due to the theoretical risk of worsening DIC and the increasing risk of ICH with lysis of leukemic promyelocytes Blum and Porcu 2007 ; Szczepiorkowski et al. 2007 ; Sanz et al. 2009 ; Szczepiorkowski et al. 2010 ; Zuckerman et al. 2012 ; Kim and Sloan 2013 ; Schwartz et al. 2013 . Data to support this contraindication are limited to one small study in which a majority of patients undergoing leu- kapheresis for HL had an adverse event that was not temporally related to the leukapheresis pro- cedure Vahdat et al. 1994 ; Tallman and Altman 2009 . Strauss et al. 1985 successfully per- formed exchange transfusion on a 2-year-old child with APL and a presenting WBC count of 617 × 10 9 L. Zuckerman et al. 2012 recom- mend leukapheresis in symptomatic adult AML patients with WBC 50 × 10 9 L and in symptom- atic ALL and CML adult patients with WBC 150 × 10 9 L. Additionally, although stating a lack of evidence, they recommend leukapheresis in asymptomatic adult AML patients with WBC 100 × 10 9 L to prevent leukostasis and asymp- tomatic adult ALL patients with WBC 300 × 10 9 L to prevent TLS. Whether leukapheresis is an effective modality to reduce early mortality is controversial. McCarthy et al. 1997 studied 48 unselected adult and pediatric patients with WBC 100 × 10 9 L who were leukoreduced and found no statistical difference in early mortality rate compared with similar unselected patients who were not leukoreduced. Porcu et al. 1997 simi- larly showed that effective leukapheresis did not impact early mortality in adult patients, especially those presenting with symptoms of leukostasis. Additional adult studies, mainly with AML patients, have had similar fi ndings Tan et al. 2005 ; Chang et al. 2007 ; De Santis et al. 2011 . Others have found a signifi cant improvement in early death rate in adult AML cohorts receiving leukapheresis without impact on overall survival Thiébaut et al. 2000 ; Giles et al. 2001 ; Bug et al. 2007 . Although multiple case reports and case series are available in the pediatric literature in regard to the effectiveness of exchange transfu- sion and leukapheresis in HL, signifi cant pediatric data on resultant early mortality and long-term outcomes, especially in AML, are lacking Carpentieri et al. 1979 ; Kamen et al. 1980 ; Shende et al. 1981 ; Warrier et al. 1981 ; Del Vasto et al. 1982 ; Strauss et al. 1985 ; Bunin et al. 1987 ; Sykes et al. 2011 . Potential complications from apheresis procedures, especially in children, must also be considered, and such procedures should only be performed in specialized centers Michon et al. 2007 .

6.8 Other Treatment Modalities

for Cytoreduction Many older studies have utilized more conserva- tive measures with success in cytoreduction for patients with HL. Such interventions may have a non-inferior impact on early death as compared to more invasive and expensive interventions such as leukapheresis.

6.8.1 Hyperhydration

Randomized controlled trials are lacking in regard to the benefi ts of hyperhydration although multiple small studies, especially in pediatric ALL, have shown signifi cant decre- ment in the WBC count with hydration alone, obviating the need for leukapheresis Maurer et al. 1988 ; Lascari 1991 ; Nelson et al. 1993 , Basade et al. 1995 .

6.8.2 Hydroxyurea

Berg et al. 1979 reported on an adult cohort of 87 AML patients who were pretreated with large doses of hydroxyurea and found no difference in early death or long-term outcome in those with and without HL. Hydroxyurea was effective in rapidly lowering the WBC count in the majority of patients. Grund et al. 1977 similarly showed that hydroxyurea was effective in decreasing WBC count in a small cohort of adult patients with acute leukemia.

6.8.3 Cranial Irradiation

Cranial radiotherapy has been noted as an effec- tive cytoreductive technique for intracerebral leukostasis in both children and adult patients Gilchrist et al. 1981 ; Ferro et al. 2014 . Ferro et al. 2014 successfully utilized whole-brain radiation therapy to alleviate neurologic symp- toms in an adult cohort with AML and HL. Maurer et al. 1988 showed no benefi t of cranial irradiation in a pediatric ALL cohort with WBC 200 × 10 9 L. Chang et al. 2007 utilized cranial irradiation and leukapheresis in adult patients with AML and HL and found no decrease in acute ICH or improved survival. Due to long- term neurologic sequelae, especially in young patients i.e., 6 years, and risk for secondary malignancy, cranial irradiation has fallen out of favor New 2001 .

6.9 Other Supportive Care

Considerations

6.9.1 Potential Laboratory

Discrepancies

6.9.1.1 Pseudohyperkalemia Hyperleukocytosis has been noted to cause pseudo-

hyperkalemia due to increased fragility of blasts leading to cell rupture and increased potassium in the plasma sample. Cell lysis can occur secondary to minor mechanical stress such as pneumatic tube transport, prolonged tourniquet placement, vacu- tainer collection, manual shaking or centrifugation. Delayed analysis can also lead to hyperkalemia. Venous blood gas samples are a simple way to avoid such spurious results Dimeski and Bird 2009 .

6.9.1.2 Pseudohypoxemia Due to the rapid consumption of oxygen by leu-

kemic blasts, it is vital that blood gas samples be kept on ice and analyzed immediately to prevent spurious results Fox et al. 1979 ; Hess et al. 1979 ; Shohat et al. 1988 ; Charoenratanakul and Loasuthi 1997 . Generally the patient’s clinical condition and pulse oximetry reading will corre- late, obviating the need for blood gas measure- ment. Gartrell and Rosenstrauch 1993 note that methemoglobinemia may be underreported at diagnosis in patients with HL; modern pulse oximetry should correlate with blood gas results in these cases.