Leukapheresis Supportive Care in Pediatric Oncology irantextbook.ir 93df

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.

6.9.1.3 Pseudohypoglycemia Consumption of glucose by excess leukocytes

can lead to pseudohypoglycemia in patients with HL Elrishi et al. 2010 . Samples that are kept cold and run promptly can avoid this potential spurious result.

6.9.1.4 Pseudothrombocytosis Leukemic blast lysis can lead to cell fragmenta-

tion which automated counters may read as plate- lets leading to an artifi cial increase in the platelet count. Since DIC is a common presentation with HL and platelet transfusion may be required to prevent bleeding with underlying true thrombo- cytopenia, it is important to examine the periph- eral smear if the automated platelet count reading does not correlate with previous values or the sta- tus of the patient.

6.9.2 Transfusion Practice with

Underlying Hyperleukocytosis As described by Lichtman 1973 , blood viscosity is usually unaltered in HL secondary to a decrease in the erythrocrit concomitant with the increased leukocrit. Therefore, blood transfusion should be avoided as it can lead to increased risk of leukosta- sis by increasing blood viscosity. Harris 1978 noted that the mean hemoglobin concentration was signifi cantly higher in adult AML patients who suf- fered an early death with three patients dying soon after blood transfusion. Therefore, asymptomatic patients should not be transfused and in general hemoglobin concentration should be maintained below 10 gdL Harris 1978 . Evidence regarding this recommendation in ALL patients is less clear Lowe et al. 2005 ; Vaitkevičienė et al. 2013 .

6.9.3 Anesthetic Procedures

Due to the risk of pulmonary complications, anesthesia should be undertaken with extreme care in the patient with HL but is often required due to the need for diagnostic procedures such as lumbar puncture and bone marrow aspiration. Fong et al. 2009 retrospectively reviewed 52 pediatric cases with HL that required anesthesia; 3 children required postanesthesia intensive care and 13 had less serious adverse events, all of a respiratory nature. In patients with respiratory distress or mediastinal mass at presentation, con- sideration should be given for utilizing peripheral blood for leukemia cytomorphology and cytoge- netics rather than bone marrow aspiration Vaitkevičienė et al. 2013 .

6.10 Summary

Although signifi cant gains have been made in the treatment of pediatric leukemia, notably ALL, APL, and CML, HL continues to pose risk both in regard to early death and decreased long-term survival. An evidence basis for sup- portive care guidelines is lacking in HL; yet, even without such consensus, intensive support- ive care has signifi cantly improved early death, especially in AML patients. Many patients who ultimately have early death present with fea- tures, chiefl y ICH, for which no intervention will likely improve survival. Additionally, many therapies that have been suggested have no impact on overall survival; in fact, secondary to the underlying aggressive phenotypes, the over- all survival is often shorter with HL. Based on the available evidence, we present our recom- mendations in Table 6.1 . In general, prompt cor- rection of coagulopathy, hypofi brinogenemia, thrombocytopenia, and hyperuricemia and rapid initiation of hydration and antileukemic therapy are vital management strategies for all patients with HL. References Azoulay É, Canet E, Raffoux E et al 2012 Dexamethasone in patients with acute lung injury from acute mono- cytic leukaemia. Eur Respir J 39:648–653 Basade M, Dhar AK, Kulkarni SS et al 1995 Rapid cyto- reduction in childhood leukemic hyperleukocytosis by conservative therapy. Med Pediatr Oncol 25:204–207 Berg J, Vincent PC, Gunz FW 1979 Extreme leucocyto- sis and prognosis of newly diagnosed patients with acute non-lymphocytic leukaemia. Med J Aust 1: 480–482