Acute Promyelocytic Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df

of subsequent HL as well as severe pulmonary or CNS symptoms Wiley and Firkin 1995 ; Sanz et al. 2005 , 2009 ; Tallman and Altman 2009 Randomized data are lacking. The use of leuka- pheresis in APL with HL is controversial and dis- cussed in Sect. 6.7 .

6.5 Chronic Myelogenous

Leukemia HL is reported to be more common in pediatric patients with CML as compared to adults Rowe and Lichtman 1984 ; Millot et al. 2005 . Even with the high WBC counts at presentation, preva- lence of leukostasis secondary to pediatric CML is thought to be uncommon although it was seen frequently in the small review by Rowe and Lichtman 1984 . Symptoms of leukostasis in CML patients can include neurologic complaints such as papilledema, cranial nerve defects, and tinnitus, respiratory complaints, and priapism Rowe and Lichtman 1984 . Priapism has been noted in pediatric ALL and CML Castagnetti et al. 2008 ; Vaitkevičienė et al. 2013 . Management of HL in CML prior to the initiation of tyrosine kinase inhibitor therapy can be accomplished with hydroxyurea Schwartz and Canellos 1975 . Management of pediatric patients with signs and symptoms of leukostasis lacks an evidence basis in the literature although sources recommend utilization of chemotherapy in addition to leukapheresis Rowe and Lichtman 1984 ; Castagnetti et al. 2008 . For low-fl ow ischemic priapism in particular, adult guide- lines recommend chemotherapy, leukapheresis, and urologic therapy with therapeutic aspiration and intracavernous sympathomimetics if aspira- tion alone is not successful Montague et al. 2003 ; Rogers et al. 2012 . Castagnetti et al. 2008 suggest patients can be managed without invasive urologic procedures utilizing chemo- therapy and leukapheresis alone; however, their small cohort required a long period of time to recover from priapism and half did not receive leukapheresis. In addition they recommend the use of anticoagulation with low-molecular- weight heparin especially with concomitant thrombocytosis although signifi cant evidence on utility is lacking. On long-term follow-up, none of their patient cohort had developed clinical evi- dence of erectile dysfunction.

6.6 Management of Tumor

Lysis Syndrome The general management of tumor lysis syn- drome TLS is discussed in Chap. 3 . Patients with HL are at increased risk of both laboratory and clinical TLS, especially those with ALL. Truong et al. 2007 showed that WBC 20 × 10 9 L was an independent risk factor for the development of TLS in pediatric ALL. Montesinos et al. 2008 similarly reported that WBC 25 × 10 9 L was an independent risk factor for TLS in adult AML patients, but it is unclear if TLS is a signifi cant issue in pediatric AML even with HL Inaba et al. 2008 ; Sung et al. 2012 . Prevention through the utilization of hyperhydra- tion, urine alkalinization, and allopurinol are all proven methods to reduce the risk of metabolic complications in pediatric patients with HL and ALL Maurer et al. 1988 ; Lascari 1991 . Maurer et al. 1988 showed no benefi t in preventing metabolic derangement through the use of low- dose prednisone prior to initiation of induction chemotherapy in pediatric ALL patients with WBC 200 × 10 9 L. The most recent expert TLS guidelines list both ALL and AML with concomitant HL as high-risk for the development of TLS and recom- mend prophylactic use of rasburicase in addition to aggressive hydration to prevent hyperuricemia Cairo et al. 2010 . These recommendations con- curred with the Italian consensus guidelines for ALL, although in the Italian opinion TLS was rare in AML even with HL and therefore should not be considered high-risk Tosi et al. 2008 . Cairo et al. 2010 recommend one dose of rasburicase at a dose of 0.1–0.2 mgkg prior to the initiation of therapy, while Tosi et al. 2008 recommend con- tinuing daily therapy at a dose of 0.2 mgkgday for 3–5 days. Additionally, the concomitant use of allopurinol due to the very rarely reported pre- cipitation of uric acid precursor xanthine and 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